Name: 99-03-6|1-(3-Aminophenyl)ethanone|98%
Brand: Ambeed
SKU: A136182
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1
[ 108-24-7 ]
[ 99-03-6 ]
[ 7463-31-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	In dichloromethane at 20℃; Inert atmosphere;
99%	With pyridine at 20℃; for 1h;
96.8%	In toluene at 20 - 55℃; for 1h;	1 Example 1; Preparation of N-(3-Acetylphenyl)acetamide To a suspension of 3' - aminoacetophenoe (50. 9 g, 377 mmol) in toluene (250 ml) was added dropwise acetic anhydride (39. 6 g, 388 mmol) at room temperature, and the mixture was kept at 55°C for one hour and then cooled to a temperature not more than 20°C. The crystals separated were filtered to give the objective compound (64.58 g ; 96. 8% yield) as a pale yellow powder.

95%	With zinc(II) oxide at 20℃; for 0.25h;
92%	Stage #1: acetic anhydride; 1-(3-aminophenyl)ethanone In ethyl acetate at 20℃; for 7h; Inert atmosphere; Stage #2: With potassium carbonate In ethyl acetate at 20℃; Inert atmosphere;
92%	With pyridine for 0.5h; Heating;
90%	In neat (no solvent) at 20℃; for 0.133333h;	Catalytic tests General procedure: Alcohol, phenol, and/or amine (1 mmol) were added to amixture of the ZnAl2O4SiO2 nanocomposite (100 mg) andacetic anhydride (1 mmol). The mixture was stirred at 75 °C(for alcohols and phenols) or at room temperature (for amines)for a time. The progress of the reaction was monitored by TLCand/or GC-MS. When the reaction was completed, ethyl acetate(10 mL) was added and the mixture was filtered to separate offthe catalyst. The catalyst was washed twice with 7.5 mL ethylacetate. The combined organic phases were washed with a10% solution of NaHCO3 and then dried over MgSO4. The solventwas removed to yield the product. If further purificationwas needed, the product was passed through a short column ofsilica gel. All products were characterized on the basis ofGC-MS, FT-IR, and 1H-NMR spectral data by comparing thesespectra with those of standard samples or literature data.
88%	With ZnAl₂O₄ nanoparticles at 20℃; for 0.166667h; Neat (no solvent);
82.8%	With triethylamine In toluene at 20 - 40℃; for 2h;	2 Example 2; Preparation of N- (3-acetylphenyl) acetamide To a mixture of 3'-aminoacetophenone (10.0 g, 74.0 mmol), triethylamine (8. 98 g, 88.8 mmol) and toluene (50 ml) was added dropwise acetic anhydride (8.31 g, 81.4 mmol) at room temperature, and the mixture was kept at 30 to 40°C for 2 hours. The crystals separated were filtered at room temperature to give the objective compound (10.86 g; 82. 8% yield) as a pale yellow powder.
72%	at 0 - 70℃; Inert atmosphere;
	With acetic acid
	at 30℃; for 1h;	4.2.2.1 Acetylation 40mmol of the appropriated amine was added carefully over 50mL of ice cooled acetic anhydride to avoid the temperature surpasses 30°C. After 1h, 200mL of cold distilled water was added, and the precipitated was filtered out and recrystallized from 40mL of ethanol. Mean yield of approximately 60%.
	With dmap In dichloromethane at 20℃;
	With copper(ll) bromide In dichloromethane at 20℃;	9 4.1.5.9. N-(3-(2-((3-(methylthio)phenyl)amino)thiazol-4-yl)phenyl)acetamide (4 i). 1-(3-aminophenyl)ethanone (50 mg, 0.37 mmol) was dissolved in CH2Cl2 (600 ml) then acetic anhydride (42 ml, 0.45 mmol) was added. The reaction was stirred at room temperature upon completeness. The reaction mixture was washed with 0.1N sodium carbonate, the organic phase was concentrated in vacuum and resuspended in ethyl acetate (1 ml) and CuBr2 (99 mg, 0.3 mmol) was added. The mixture was then stirred at reflux overnight. The organic phase was washed with H2O (2 x 2 ml),concentrated to obtain 1-(3-aminophenyl)-2-bromoethanone. The bromoketone (64 mg, 0.3 mmol) was resuspended in anhydrous EtOH (1 ml) and conjugated with 1-(3-(methylthio)phenyl)thioureaa (59 mg, 0.3 mmol) as previously described. The final product was purified by preparative HPLC, the peak of interest was concentrated to obtain the title compound. (96 mg, 73%) 1H NMR (300 MHz, CDCl3) δ 7.95-7.89 (m 1H), 7.60-7.50 (d, J 7.7 Hz, 2H), 7.40-7.29 (m, 3H), 7.24 (t, J 8.0 Hz, 1H), 7.10 (ddd, J 8.1, 2.2, 0.8 Hz, 1H), 6.93 (ddd, J 7.81.6, 0.9 Hz, 1H), 6.83 (s, 1H), 2.43 (s, 3H), 2.17 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 168.5, 164.3, 150.7, 140.9, 140.3 ,138.3, 135.2, 129.8, 129.5, 122.1, 121.0, 119.6, 117.6, 115.7, 114.8, 102.7, 24.8, 15.7. ESI-MS m/z: 356.1 [M+H]+.
6.39 g	In toluene at 20 - 55℃; for 3h;	87 Reference Production Example 87 Reference Production Example 87 (0853) To a mixture of 50 mL of toluene and 6.76 g of 3-aminoacetophenone, 4.7 mL of acetic anhydride was added dropwise, followed by stirring at room temperature for 2 hours and further heating and stirring at 55°C for one hour. After cooling to room temperature, filtration, and washing with toluene, the obtained residue was dried under reduced pressure to obtain 6.39 g of N-(3-acetylphenyl)acetamide (C87A). 1H-NMR (CDCl3) δ (ppm): 8.00 (1H, s), 7.92 (1H, d, J = 8.2 Hz), 7.69 (1H, d, J = 7.8 Hz), 7.61 (1H, bs), 7.43 (1H, t, J = 7.9 Hz), 2.61 (3H, s), 2.22 (3H, s).
	at 20℃; for 2h;	33.a A) 3-Aminoacetophenone (50 g, 370 mmol) was dissolved in acetic anhydride (35 mL, 370 mmol) and stirred at room temperature for 2 hours. The acetic anhydride was evaporated under reduced pressure to give white crystals which were taken directly without further purification.
	In dichloromethane at 0 - 20℃; Inert atmosphere;
	With dmap In dichloromethane

Reference： [1]Zhao, Lele; Cao, Danyan; Chen, Tiantian; Wang, Yingqing; Miao, Zehong; Xu, Yechun; Chen, Wuyan; Wang, Xin; Li, Yanlian; Du, Zhiyan; Xiong, Bing; Li, Jian; Xu, Chunyan; Zhang, Naixia; He, Jianhua; Shen, Jingkang [Journal of Medicinal Chemistry, 2013, vol. 56, # 10, p. 3833 - 3851]
[2]Shaikh, Ajam C.; Chen, Chinpiao [Journal of labelled compounds and radiopharmaceuticals, 2008, vol. 51, # 1, p. 72 - 76]
[3]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - WO2004/87637, 2004, A1 Location in patent: Page 16
[4]Hosseini Sarvari, Mona; Sharghi, Hashem [Tetrahedron, 2005, vol. 61, # 46, p. 10903 - 10907]
[5]Location in patent: experimental part Temperini, Andrea; Terlizzi, Raffaella; Testaferri, Lorenzo; Tiecco, Marcello [Synthetic Communications, 2010, vol. 40, # 2, p. 295 - 302]
[6]Location in patent: experimental part Vogl, Michael; Kratzer, Regina; Nidetzky, Bernd; Brecker, Lothar [Organic and Biomolecular Chemistry, 2011, vol. 9, # 16, p. 5863 - 5870]
[7]Farhadi, Saeed; Jahanara, Kosar [Cuihua Xuebao/Chinese Journal of Catalysis, 2014, vol. 35, # 3, p. 368 - 375]
[8]Location in patent: scheme or table Farhadi, Saeid; Panahandehjoo, Somayeh [Applied Catalysis A: General, 2010, vol. 382, # 2, p. 293 - 302]
[9]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - WO2004/87637, 2004, A1 Location in patent: Page 16
[10]Pialat, Amelie; Liegault, Benoit; Taillefer, Marc [Organic Letters, 2013, vol. 15, # 7, p. 1764 - 1767]
[11]Rupe; Braun; v. Zembrzuski [Chemische Berichte, 1901, vol. 34, p. 3522]
[12]Blau, Lorena; Menegon, Renato Farina; Trossini, Gustavo H. G.; Molino, João Vitor Dutra; Vital, Drielli Gomes; Cicarelli, Regina Maria Barretto; Passerini, Gabriela Duó; Bosquesi, Priscila Longhin; Chin, Chung Man [European Journal of Medicinal Chemistry, 2013, vol. 67, p. 142 - 151]
[13]Zhang, Yu-Juan; Shen, Liu-Lan; Cheon, Hyae-Gyeong; Xu, Yong-Nan; Jeong, Jin-Hyun [Archives of Pharmacal Research, 2014, vol. 37, # 5, p. 588 - 599]
[14]Pesce, Emanuela; Bellotti, Marta; Liessi, Nara; Guariento, Sara; Damonte, Gianluca; Cichero, Elena; Galatini, Andrea; Salis, Annalisa; Gianotti, Ambra; Pedemonte, Nicoletta; Zegarra-Moran, Olga; Fossa, Paola; Galietta, Luis J.V.; Millo, Enrico [European Journal of Medicinal Chemistry, 2015, vol. 99, p. 14 - 35]
[15]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - EP2927218, 2015, A1 Location in patent: Paragraph 0853
[16]Current Patent Assignee: Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - CN103833671, 2016, B Location in patent: Paragraph 0129; 0130; 0131; 0132
[17]Ghosh, Chiranjit; Nagtilak, Prajyot Jayadev; Kapur, Manmohan [Organic Letters, 2019]
[18]Current Patent Assignee: SOUTHERN UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA - CN110627610, 2019, A Location in patent: Paragraph 0383

2
[ 99-03-6 ]
[ 110-13-4 ]
1-(3-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With oxalic acid In ethanol at 60℃; for 0.5h; Green chemistry;	General procedure forthepreparation of2,5-dimethylpyrroles General procedure: In a typical reaction, primary aromatic amine (1 mmol), hexane-2,5-dione (1.2 mmol) and a naturally occurring organic acid (0.2 mmol) were dissolved in ethanol (2mL) and stirred at 60°C for an appropriate reaction time. After completion of the reaction (monitored by GC), water (2×10mL) was added to the reaction mixture in order to remove the catalyst. The obtained solution was extracted by ethyl acetate (2×5mL), and the organic layer was separated and dried over Na2SO4. The separated organic phase was evaporated under reduced pressure to give the corresponding pyrrole. In cases where the reaction did not proceed to completeness, crude product was purifed by recrystallization (in ethanol) or by column chromatography [ethyl acetate/petroleum ether (3:7)] to give the pure product 1. All products 1ar are known compounds, and their structures were confrmed by melting point and/or identifed by comparison of their GC and GC/MS with those of authentic samples reported in our previous papers.
93%	With salicylic acid In neat (no solvent) for 0.166667h; Microwave irradiation;	2.1 Procedure for the preparation of 2,5-dimethylpyrroles General procedure: A laboratory microwave oven MW 3100 (LandgrafLaborsysteme HLL GmbH, Langenhagen, Germany)equipped with a magnetic stirrer operating at 2450 MHz was used for synthesis of pyrrole derivatives.In a typical reaction, primary amine (1.0 mmol),hexane-2,5-dione (1.2 mmol) and salicylic acid(0.02 g, 0.15 mmol) were taken in an open vessel and irradiated for an appropriate time and monitored by GC. Water (20 mL) was added to the reaction mixture and stirred for 10 min. The mixture was then extracted by ethyl acetate (2 9 5 mL) and the organic layer was separated and dried over Na2SO4. The solvent wasthen evaporated under reduced pressure to obtain the corresponding product. In those cases where thereaction did not proceed to the completeness, the crudeproduct was passed through a short column of neutralalumina [eluted with ethyl acetate/petroleum ether(3:7)] to give the pure pyrrole 1
	With acetic acid

Reference： [1]Mohsenzadeh, Farshid; Darabi, Hossein Reza; Alivand, Mahsa; Aghapoor, Kioumars; Balavar, Yadollah [Research on Chemical Intermediates, 2020, vol. 46, # 12, p. 5255 - 5262]
[2]Aghapoor, Kioumars; Mohsenzadeh, Farshid; Darabi, Hossein Reza; Sayahi, Hani [Journal of Chemical Sciences, 2021, vol. 133, # 2]
[3]Buu-Hoi [Journal of the Chemical Society, 1949, p. 2882,2886]

3
[ 99-03-6 ]
[ 79-04-9 ]
[ 42865-69-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine In dichloromethane at 20℃; for 0.5h;	Synthetic procedure for N-(3-acetylphenyl)-2-chloroacetamide (3) To the solution (1 mmol) of 3-aminoacetopheneone (1) and(1 mmol) of 2-chloroacetyl chloride (2) in TEA (3 ml) followedby DCM (10 ml), the reaction mixture was stirred at roomtemperature. After completing the reaction monitored byTLC, the solid was washed with ethanol-water to get crudeproducts N-(3-acetylphenyl)-2-chloroacetamide 3 (92%) yield. Colourless solid; m.p. 186-182 °C; 1H NMR(300 MHz CDCl3): δ 2.61 (s, 3H), 4.21 (s, 2H), 7.44 (t,1H, J = 7.8 Hz), 7.74 (d, 1H, J = 7.8 Hz), 7.90 (d, 1H, J =7.8 Hz), 8.05 (s, 1H), 8.48 (s, 1H). ESI-MS (M+ +1)calculated m/z 211.64 Found 212.04 Anal. Calcd for:C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62% found: C,56.24; H, 4.72; N, 6.60%.
71%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h;	4.1.1. N-(3-Acetyl-phenyl)-2-chloroacetamide (6a) A mixture of 3-aminoacetophenone (5a) (1.35 gm, 0.01 mol), chloroacetylchloride (0.8 mL, 0.01 mol) and anhydrous potassium carbonate(1.38 gm, 0.01 mol) in dry dimethylformamide was stirred at room temperaturefor 24 h. The reaction mixture was poured into ice-cold water andthe separated product was filtered, dried and crystallized from benzene togive 6a (1.5 g, 71%) as a buff powder: mp 188-200 °C; IR (film) 3447(NH), 3043 (CH aromatic), 2957 (CH aliphatic), 1706, 1672 (2CO) cm-1;1H NMR (DMSO-d6) δ 2.56 (s, 3H, CH3), 4.28 (s, 2H, CH2), 7.47-7.51 (m,1H, phenyl H-5), 7.69 (d, J=7.5 Hz, 1H, phenyl H-4), 7.86 (d, J=7.5 Hz,1H, phenyl H-6), 8.17 (s, 1H, phenyl H-2), 10.51 (s, 1H, NH, D2O exchangeable);13C NMR (DMSO-d6) δ 27.14 (CH3), 43.98 (CH2), 119.01(acetylphenyl C-2), 124.31 (acetylphenyl C-4), 124.34 (acetylphenyl C-6),129.76 (acetylphenyl C-5), 137.70 (acetylphenyl C-3), 139.29 (acetylphenylC-1), 165.44 (NHC=O), 198.00 (C]O); EIMS (m/z) 211 (M+.,100%). Anal. Calcd for C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62. Found: C,56.66; H, 4.60; N, 6.50.
	With sodium hydroxide; toluene

	With sodium hydroxide; benzene
	In tetrahydrofuran for 0.5h;	A solution of 3'-amino-acetophenone (25 mmol) in THF (100 mL) was added chloroacyl chloride (30 mmol). The mixture was stirred for 30 min, poured into icecold 2M NaOH (aq) and extracted with Et2O. The organic phase was dried and the solvent was removed under reduced pressure giving the pure product. A solution of the product (10 mmol) and triethyl amine (30 mmol) in ethanol was added amine (20 mmol) and the mixture was refluxed for 4 hours. Ethanol was removed under reduced pressure and the product was dissolved in EtOAc and washed with 2M NaOH (aq). EtOAc was removed under reduced pressure giving the product as pure brown oil in 85% yield. 1H-NMR (CDCl3) No. 9.31 (s, 1H), 8.05 (m, 2H), 7. 72 (dt, 1H), 7.46 (t, 1H), 3.11 (s, 2H), 2.62 (s, 3H), 2.41 (s, 6H).
	With glacial acetic acid at 0 - 20℃; for 4h;
	With triethylamine In dichloromethane
	With anhydrous Sodium acetate; glacial acetic acid In lithium hydroxide monohydrate at 20℃; for 4h;
	Stage #1: 1-(3-aminophenyl)ethan-1-one With Sodium hydrogenocarbonate In chloroform at 20℃; for 0.25h; Stage #2: chloroacetyl chloride In chloroform at 20℃; for 2h;
	With triethylamine In dichloromethane
	With triethylamine In dichloromethane at 0 - 5℃; for 5h;
	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	1.1 General procedure for synthesis of 2-chloro-N-arylacetamide (4a-c) General procedure: Chloroacetyl chloride (1 mL, 13.3 mmol, 1.2 equiv.) diluted in 5 mL CH2Cl2 was added dropwise to a mixture of acetyl substituted aniline 3a-c (1 equiv., 11.1 mmol) and Et3N (2.3 mL, 16.7 mmol, 1.5 equiv.) in 30 mL anhydrous CH2Cl2 at 0 C. The reaction mixture was warmed to rt and stirred for an additional 3-4 h under inert atm. After completion of reaction as monitored by TLC (EtOAc:Hex 1:4), the solvent was removed under reduced pressure. The residue thus obtained was washed repeatedly with petroleum ether to provide crude 4a-c as white to off-white crystals (82-88%) that was used without any further purification and characterization.
	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	1.1 General procedure for synthesis of 2-chloro-N-arylacetamide (4a-c) General procedure: Chloroacetyl chloride (1 mL, 13.3 mmol, 1.2 equiv.) diluted in 5 mL CH2Cl2 was added dropwise to a mixture of acetyl substituted aniline 3a-c (1 equiv., 11.1 mmol) and Et3N (2.3 mL, 16.7 mmol, 1.5 equiv.) in 30 mL anhydrous CH2Cl2 at 0 C. The reaction mixture was warmed to rt and stirred for an additional 3-4 h under inert atm. After completion of reaction as monitored by TLC (EtOAc:Hex 1:4), the solvent was removed under reduced pressure. The residue thus obtained was washed repeatedly with petroleum ether to provide crude 4a-c as white to off-white crystals (82-88%) that was used without any further purification and characterization.

Reference： [1]Lakshmanan, Sivalingam; Govindaraj, Dharman; Mahalakshmi; Thirumurugan; Ramalakshmi; Antony, S. Arul [Structural Chemistry, 2021, vol. 32, # 4, p. 1597 - 1609]
[2]Bakr, Rania B.; Ghoneim, Amira A.; Azouz, Amany A. [Bioorganic Chemistry, 2019, vol. 88]
[3]Jacobs; Heidelberger [Journal of Biological Chemistry, 1915, vol. 21, p. 150]
[4]Jacobs; Heidelberger [Journal of Biological Chemistry, 1915, vol. 21, p. 150]
[5]Moghaddam, Firouz Matloubi; Hojabri, Leila [Journal of Heterocyclic Chemistry, 2007, vol. 44, # 1, p. 35 - 38]
[6]Current Patent Assignee: LICA PHARMACEUTICALS - WO2003/97574, 2003, A2 Location in patent: Page/Page column 34
[7]Location in patent: scheme or table Liu, Wukun; Hua, Jie; Zhou, Jinpei; Zhang, Huibin; Zhu, Haiyang; Cheng, Yanhua; Gust, Ronald [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 15, p. 5008 - 5012]
[8]Saeidian, Hamid; Mirjafary, Zohreh; Abdolmaleki, Elinaz; Moradnia, Farzaneh [Synlett, 2013, vol. 24, # 16, p. 2127 - 2131]
[9]Inam, Afreen; Van Zyl, Robyn L.; Van Vuuren, Natasha J.; Chen, Chien-Teng; Avecilla, Fernando; Agarwal, Subhash M.; Azam, Amir [RSC Advances, 2015, vol. 5, # 60, p. 48368 - 48381]
[10]Li, Qi; Chen, Ying; Xing, Shuaishuai; Liao, Qinghong; Xiong, Baichen; Wang, Yuanyuan; Lu, Weixuan; He, Siyu; Feng, Feng; Liu, Wenyuan; Chen, Yao; Sun, Haopeng [Journal of Medicinal Chemistry, 2021, vol. 64, # 10, p. 6856 - 6876]
[11]Fang, Zi-Mian; Guo, Deng-Xuan; Ji, Jin; Liu, Li-Wei; Qi, Pu-Ying; Shao, Wu-Bin; Wang, Jin-Jing; Wang, Pei-Yi; Yang, Song; Zhou, Xiang [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 50, p. 15108 - 15122]
[12]Nazir, Yasir; Rafique, Hummera; Roshan, Sadia; Shamas, Shazia; Ashraf, Zaman; Rafiq, Muhammad; Tahir, Tehreem; Qureshi, Zia-Ur-Rahman; Aslam, Alvina; Asad, Muhammad Hassham Hassan Bin [BioMed Research International, 2022, vol. 2022]
[13]Chopra, Sidharth; Dasgupta, Arunava; Kaul, Grace; Kumar Sahoo, Santosh; Maddipatla, Sarvan; Madhavi Yaddanapudi, Venkata; Nageswara Rao Gajula, Siva; Naiyaz Ahmad, Mohammad; Nanduri, Srinivas; Sonti, Rajesh [Bioorganic and Medicinal Chemistry, 2022, vol. 64]
[14]Chopra, Sidharth; Dasgupta, Arunava; Kaul, Grace; Kumar Sahoo, Santosh; Maddipatla, Sarvan; Madhavi Yaddanapudi, Venkata; Nageswara Rao Gajula, Siva; Naiyaz Ahmad, Mohammad; Nanduri, Srinivas; Sonti, Rajesh [Bioorganic and Medicinal Chemistry, 2022, vol. 64]

4
[ 99-03-6 ]
[ 14452-30-3 ]

Yield	Reaction Conditions	Operation in experiment
64%	With toluene-4-sulfonic acid; sodium iodide In water; acetonitrile at 10 - 20℃; for 2h; Inert atmosphere;
63%	Stage #1: 1-(3-aminophenyl)ethanone With sulfuric acid; copper; copper(II) sulfate; potassium iodide In water for 2h; Reflux; Stage #2: With sodium nitrite In water at 80 - 90℃;
	With hydrogenchloride; potassium iodide

Multi-step reaction with 2 steps 1.1: HCl; NaNO₂ / H₂O / 0.5 h / 0 °C 1.2: 93 percent / K₂CO₃ / H₂O; acetonitrile / 0.5 h / 0 °C 2.1: 83 percent / MeI / 24 h / 120 °C

Reference： [1]Sloan, Nikki L.; Luthra, Sajinder K.; McRobbie, Graeme; Pimlott, Sally L.; Sutherland, Andrew [RSC Advances, 2017, vol. 7, # 86, p. 54881 - 54891]
[2]Location in patent: experimental part Vogl, Michael; Kratzer, Regina; Nidetzky, Bernd; Brecker, Lothar [Organic and Biomolecular Chemistry, 2011, vol. 9, # 16, p. 5863 - 5870]
[3]Lutz et al. [Journal of Organic Chemistry, 1947, vol. 12, p. 617,680] Evans; Morgan; Watson [Journal of the Chemical Society, 1934, p. 1167,1169]
[4]Liu, Ching-Yuan; Ren, Hongjun; Knochel, Paul [Organic Letters, 2006, vol. 8, # 4, p. 617 - 619]

5
[ 99-03-6 ]
[ 121-71-1 ]

Yield	Reaction Conditions	Operation in experiment
88.3%	Stage #1: 1-(3-aminophenyl)ethanone With sulfuric acid In water at 45 - 50℃; for 0.5h; Stage #2: With water; urea; sodium nitrite In water at 0 - 5℃; for 0.5h; Stage #3: With sulfuric acid In 5,5-dimethyl-1,3-cyclohexadiene; water at 90℃; for 2h;	1.S3 S3. Diazotization and Hydrolysis Reaction In the reactor,Add 590g of water,270g mass fraction of 98% concentrated sulfuric acid,135 g (1 mol) of 3-aminoacetophenone prepared by S2 was added thereto at a controlled temperature of 45 to 50 ° C,Insulation stirring 0.5h,Control the temperature at 0 ~ 5 ,Dropping sodium nitrite solution (sodium nitrite 77g and 190g water preparation,The mass fraction is 28.8%All drops),After the addition is completed,Add 2.8g of urea,Insulation diazotization reaction 0.5h,After completion of the reaction was added to the reaction solution from xylene,Water and concentrated sulfuric acid mixture of hydrolyzate (380g of xylene, 80g of water and 16g concentrated sulfuric acid),Heated to 90 hydrolysis reaction,Nitrogen release,Reflux 2h,After the completion of the hydrolysis reaction was cooled to 10 ~ 15 ,Insulation stirring 0.5h,filter,Washed,Dried to give pale yellow powder 3-hydroxyacetophenone 120g,The yield was 88.3%The tested melting point of 95-98 ;
80%	Stage #1: 1-(3-aminophenyl)ethanone With sodium nitrite In water at 20℃; Milling; Green chemistry; Stage #2: With water at 80℃; for 0.5h; Neutral conditions; Green chemistry;	General procedure: Aniline (1mmol, 0.095mL), silica sulfuric acid (0.75g) and sodium nitrite (1.7mmol, 0.12g) were ground in a mortar with a pestle for a few minutes to obtain a homogeneous mixture. Then, four drops of water were gradually added and the mixture was ground for 10min to give phenyl diazonium silica sulfate. Five drops of water were added to phenyl diazonium silica sulfate (1mmol) and the resulting mixture was simply blended and then placed into a covered petri dish. Then, the petri dish was placed in an oven at 60°C for 15min. After that, the reaction mixture was diluted with EtOAc (15mL) and filtered after vigorous stirring. The residue was extracted with EtOAc (2×10mL) and the combined organic layer was dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to afford the crude product. Further purification was performed by flash column chromatography and the pure phenol was obtained in 81% (0.076g).
58%	With uranyl nitrate hydrate; water; trifluoroacetic acid for 48h; Irradiation; Inert atmosphere;	16 Example 16 In a 25mL reaction tube, add m-acetylaniline (0.2mmol, 27.0mg), water (0.6mmol, 10.8mg), uranyl nitrate hydrate (4mol%/0.008mmol, 4mg), Trifluoroacetic acid (0.4mmol, 45.6mg), hexafluoroisopropanol (2mL), stirred for 2 days under the irradiation of a 6-watt blue LED lamp (wavelength 460nm) in a nitrogen atmosphere, after the reaction is complete, extract, concentrate, and pass through the column Analysis (VPE/VEA=10/1) isolated white solid 3p (15.8mg, 58%).

With sulfuric acid; water Diazotization;

Reference： [1]Current Patent Assignee: HUBEI SHINREZING PHARMACEUTICAL TECH - CN106242957, 2016, A Location in patent: Paragraph 0030; 0037; 0044
[2]Zarei, Amin; Khazdooz, Leila; Aghaei, Hamidreza; Gheisari, Mohammad Mehdi; Alizadeh, Shahrzad; Golestanifar, Laleh [Tetrahedron, 2017, vol. 73, # 49, p. 6954 - 6961]
[3]Current Patent Assignee: EAST CHINA NORMAL UNIVERSITY - CN112778125, 2021, A Location in patent: Paragraph 0100-0102
[4]Burkhardt; Horrex; Jenkins [Journal of the Chemical Society, 1936, p. 1649,1651] Simpson et al. [Journal of the Chemical Society, 1945, p. 646,655] Fuson; Lewis; Du Puis [Journal of the American Chemical Society, 1932, vol. 54, p. 1114,1116] Cobb [1945, vol. 25, p. 64] King; McWhirter; Barton [Journal of the American Chemical Society, 1945, vol. 67, p. 2089,2090]

6
[ 99-03-6 ]
[ 455-36-7 ]

Yield	Reaction Conditions	Operation in experiment
25%	With tert.-butylnitrite; boron trifluoride diethyl etherate; In benzonitrile; at 90℃; for 0.75h;	Examples 2 to 6; Before describing the examples in detail, the procedure which is used in all the examples is specified. An aminoaromatic compound in a solvent (o-dichlorobenzene or benzonitrile) is slowly introduced onto a BF3.Et2O heel (1.4-1.5 molar equivalents) at a temperature of less than 0 C. or onto a BF3.2H2O heel (1.4-1.5 molar equivalents) at ambient temperature in a three-necked round-bottomed flask equipped with a reflux condenser, a thermocouple and a stirring system. t-Butyl nitrite in the same solvent is then added at ambient temperature and then the reaction medium is heated at the temperature specified in the table below and according to the time shown. The results are recorded in table (I). Table I

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 5705 - 5708
[2]Patent: US2007/276168,2007,A1 .Location in patent: Page/Page column 8
[3]Journal of the Chemical Society,1935,p. 1167,1172
[4]Journal of the American Chemical Society,1963,vol. 85,p. 709 - 724

7
[ 121-89-1 ]
[ 99-03-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With cadmium sulphide; ammsnium formate In lithium hydroxide monohydrate at 20℃; for 14h; Inert atmosphere; Irradiation; Sealed tube; chemoselective reaction;
100%	With lithium hydroxide monohydrate; oxalic acid; titanium(IV) dioxide for 3h; Irradiation; Inert atmosphere; Sealed tube; Green chemistry; chemoselective reaction;	General procedure: Nitro compounds (0.1 mmol under sunlight and 0.5 mmol under UV LED irradiation) were dissolved in PEG-400 (1.5 ml) and then 10 ml of water was added to the solution; commercial TiO2 (P25) (40 mg) and oxalic acid (1.5 equimolar) were added into a round bottom Pyrex flask (25 ml). The reaction mixture was degassed by Argon gas (20 min) and sealed with a septum. Afterwards, the flask was irradiated under stirring with sunlight or violet LED (see the data in Table 2). After the completion of the reaction according to GC monitoring, NaHCO3 was added to increase pH = 7 and the mixture was stirred at room temperature. The aqueous layer was extracted with EtOAc (2x10 ml). The organic layer was dried with sodium sulfate, filtered and evaporated in vacuum.
99%	With hydrogen In methanol at 70℃; for 4h;	1 Embodiment 1 The 2.0g nitro-acetophenone between, 0.2gPt/Bi2O3(Pt content is 0.2 wt %), 10 ml anhydrous methanol by adding 50 ml of a batch-type reactor, successively for substitution reaction of the nitrogen and hydrogen gas in the kettle 3-5 time, hydrogen is charged into the pressure to 1.0 MPa, the temperature under stirring to 70 °C, the stirring speed is 600-800 rotation/minute. If the total pressure is reduced to 0.5 MPa the following, the additional hydrogen to the initial pressure. 4h no longer changes the total pressure of the, stop stirring, cooling to room temperature. To the reaction mixture after centrifugal, is yellow at the bottom of the catalyst, is green supernatant (if a meta-nitro acetophenone conversion is not complete, then the supernatant is a yellow-green, by-product with the nitro portion of the hydrogenation product is nitroso compound). Heating a small amount of supernatant using gas chromatographic analysis, a meta-nitro acetophenone conversion is greater than 99.9%, m-aminoacetophenone selectivity is greater than 99.9% (Figure 3). Rotary evaporation of the filtrate is removed by methanol to obtain the product m-aminoacetophenone, separation yield 99%

99%	With hydrogen In ethanol at 90℃; for 2h; Autoclave;
98%	With potassium hydroxide In isopropanol at 100℃; Microwave irradiation;
98%	With hydrazine hydrate monohydrate In ethanol at 20℃; for 4h; chemoselective reaction;
98.5%	With hydrogen In o-dimethylbenzene; toluene at 90℃; for 5h; Autoclave; chemoselective reaction;
97%	With potassium fluoride; PMHS In tetrahydrofuran at 20℃; for 0.5h;
96%	With lithium hydroxide monohydrate at 20℃; Inert atmosphere; chemoselective reaction;
96%	With anhydrous silver tetrafluoroborate; 4,4'-Dimethoxy-2,2'-bipyridin; potassium-t-butoxide; hydrogen In 1,4-dioxane at 80℃; for 8h; Autoclave;	1 Example 1 A solution of 16.44 mg (0.04 mmol) 4,4'-dimethoxy-2,2'-bipyridine silver 11.22 mg (0.1 mmol) of potassuim t-butoxide and 1 mL of 1,4-dioxane were charged into an autoclave. After stirring, 165.15 mg (1 mmol) of m-nitroacetophenone was added and the mixture was stirred at 80 °C. The reaction was carried out for 8 hours. After the reaction has finishedm the reaction solution was extracted with water and dichloromethane to collect the organic phase. Then, the organic phase was dried over anhydrous Na2SO4, suction filtered, rotary evaporated and chromatographed to give a yellow solid 3-acetanilide. Yield 96 %.
96.5%	With hydrogen In tetrahydrofuran at 160℃; for 1.5h;	2.4 Typical procedure for the hydrogenation of nitroaromatics General procedure: The hydrogenation of nitroaromatics was carried out as follows. The mixture of nitroaromatics (1.5mmol), THF (5.0mL) and the AgC/ZrPP-500R catalyst (0.05g) were placed in a 25mL Schlenk flask equipped with a magnetic stirrer and purged five times with N2 to replace the air in the autoclave, five times with pure H2 to replace the N2 prior to experiments. Finally, hydrogen was added to the given pressure and the reactor was heated to 160°C with vigorous stirring. After the hydrogenation reactions, the Schlenk flask was cooled quickly to room temperature. Then the catalyst was filtrated to separate from the solution, the filtrate was added to the volumetric flask and the catalyst was washed with THF and dried at 40°C overnight and used for the next run. The liquid products were analyzed by Shimadzu GC-2014 equipped with an KB-50MS (30m long, 0.32mm i.d., 0.50μm film thickness) and an Agilent 6890/5973 GC-MS system equipped with a HP-5MS column (30m long, 0.25mm i.d., 0.25μm film thickness). The obtained products were isolated and purified by evaporation or column chromatography, and then analyzed by 1H NMR (Fig. S6-S14).
96%	With phenylsilane; triphenylphosphine; sodium iodide In chloroform at 60℃; for 72h; Inert atmosphere; Irradiation;
95%	With palladium 10% on activated carbon; ammsnium formate; mesoporous silica In methanol for 1.5h; Milling;	2. General procedure for the mechanochemical reduction of nitroarenes General procedure: In a typical experiment, a mixture of nitroarene compound (1.0 mmol),ammonium formate (3.3 mmol, 208 mg, 1.1 equivalent), palladium catalyst (10 % Pdon activated carbon, 2 mol%, 21 mg) and silica (175 mg) was ball milled in thepresence of dry methanol (η = 0.25 μL mg-1) for 90 minutes. After milling, a smallsample (≈ 1 mg) of the crude reaction mixture was suspended in methanol andimmediately analyzed by TLC (typically using dichloromethane : methanol = 20 : 1mixture as an eluent). The crude mixture was left in a well ventilated hood overnight,suspended in methanol and filtered over a Büchner funnel. Evaporation of the filtrateafforded the desired amino-derivative. If necessary, the final product was purified bycolumn chromatography.
95%	Stage #1: 3-Nitroacetophenone In lithium hydroxide monohydrate at 20℃; for 0.0833333h; Stage #2: With sodium tetrahydridoborate In lithium hydroxide monohydrate at 75℃; for 0.333333h;	2.3.4 Synthesis of amines catalyzed using CoO(at)N-mC General procedure: To a 10mL round-bottom flask equipped with a magnetic stirrer, CoO(at)N-mC nanocatalyst (30mg), nitroarene (1.0mmol), and H2O (3mL) were added and the reaction mixture was stirred at ambient temperature for 5min, then NaBH4 (3mmol) was added and the resulting mixture heated in an oil bath at 75°C for an appropriate time. After the finishing of the reduction reaction that was followed by applying TLC, CoO(at)N-mC nanocatalyst was separated with the centrifuge, rinsed with ethanol, dried at 60°C to be ready for the next cycle without any purification. After isolation of catalyst, the product was extracted with ethyl acetate and purified by short column chromatography on silica gel, if necessary, to obtain the relevant compound in desired purity.
94%	With hydrogen In isopropanol at 59.84℃; for 1.5h; Autoclave;
94%	Stage #1: 3-Nitroacetophenone With Cu(OH)x impregnated on Fe<SUB>3</SUB>O<SUB>4</SUB> In lithium hydroxide monohydrate for 0.0833333h; Green chemistry; Stage #2: With sodium tetrahydridoborate In lithium hydroxide monohydrate at 55 - 60℃; for 0.2h; Green chemistry;	A typical procedure for reduction of nitrobenzene to aniline with NaBH4/Nano Fe₃O₄-Cu(OH)_x system General procedure: In a round-bottom flask (10 mL) equipped with a magnetic stirrer, a mixture of nitrobenzene (0.123 g, 1 mmol) and H2O (3 mL) was prepared. Nano Fe3O4-Cu(OH)x(20 mg, 0.06 mmol, x = 2) was then added, and the resulting mixture was stirred for 5 min. Next, NaBH4 (0.076 g,2 mmol) was added and the reaction mixture was continued to stirring for 3 min at 55-60 °C. TLC monitored the progress of the reaction (eluent, n-hexane/EtOAc: 5/2). After completion of the reaction, the nanocatalyst was separated by an external magnet and the reaction mixture was extracted with EtOAc (2 × 5 mL). Drying organic layer over anhydrous Na2SO4 and then evaporation of the solvent affords the pure liquid aniline in 95 % yield (0.088 g, Table 2, entry 1).
94%	With sodium tetrahydridoborate; ethanol at 20℃; for 0.5h;	The general method for selective reductionof nitroarenes General procedure: This procedure includes the addition of Fe3O4 Guanidine-CuII (0.6 mol %) to nitro compound (1 mmol) and NaBH4(3 mmol) in ethanol (2 ml) within ambient conditionsand agitated for an appropriate period (Table 1).With the help of TLC, the advancement in reduction isregulated. Later, the catalyst particles were separated usingan external magnet, in addition to washing the mixturewith ethyl acetate (EtOAc) (2 × 5 ml) and H2O(3 × 5 ml).Then anhydrous Na2SO4was used to dehydrate the organiclayer and thus the solvent was evaporated to recover thecrude resultants with reduced pressure. The final step wasperformed by eluting the product with n-hexane: ethylacetate (4:1) solution in column chromatography packed with silica gel.
94%	With sodium tetrahydridoborate; ethanol at 20℃; for 0.5h;	The general method for selective reductionof nitroarenes General procedure: This procedure includes the addition of Fe3O4 Guanidine-CuII (0.6 mol %) to nitro compound (1 mmol) and NaBH4(3 mmol) in ethanol (2 ml) within ambient conditionsand agitated for an appropriate period (Table 1).With the help of TLC, the advancement in reduction isregulated. Later, the catalyst particles were separated usingan external magnet, in addition to washing the mixturewith ethyl acetate (EtOAc) (2 × 5 ml) and H2O(3 × 5 ml).Then anhydrous Na2SO4was used to dehydrate the organiclayer and thus the solvent was evaporated to recover thecrude resultants with reduced pressure. The final step wasperformed by eluting the product with n-hexane: ethylacetate (4:1) solution in column chromatography packed with silica gel.
93%	With [RuCl(η⁶-p-cymene)(benzyl N'-thiophene-2-carbonyl-N-(pyridin-2-ylmethyl)carbamimidothioate)]Cl; potassium hydroxide In isopropanol for 10h;	2.3. Procedure for catalytic TH of nitroarenes and carbonylcompounds General procedure: Substrate (1 mmol) was added to 2-propanol (4 mL) solution ofthe catalyst (0.1 mol %) and KOH (1 mmol), and refluxed at 85 C.The completion of the reaction was checked by TLC. Then, the reactionmixture was cooled to room temperature, eluted throughshort silica gel or alumina bed using 50% hexane-ethyl acetatemixture and analyzed by GC or GC-MS. The products were isolatedfrom the most of the reactions and confirmed by their 1H NMRspectra
92%	With sodium dihydrosulfite; potassium carbonate In lithium hydroxide monohydrate; acetonitrile at 35℃; for 0.5h;
92%	With hydrogen In ethyl acetate at 20℃; for 8h;
92%	With peganine In lithium hydroxide monohydrate at 120℃; for 24h; chemoselective reaction;
92%	With sodium tetrahydridoborate; lithium hydroxide monohydrate In neat (no solvent) at 20℃; for 0.0833333h; Milling;	General procedure: As a representative example, a mixture of nitrobenzene(1 mmol), Ni2BCu2O (54 mg), 1 drop of distilled water, and NaBH4 (2.5mmol) was ground using a simple porcelainmortar and pestle for 1 min at room temperature. After completion of the reaction (checked by TLC), distilled water(5mL) was added to the reaction vessel, and subsequently the reaction mixture transferred to a round-bottom flask (25mL) equipped with a magnetic stirrer. The mixture was stirredvigorously for 2min. Next, the product was extracted with dichloromethane (53mL). The extracts were dried with anhydrous sodium sulfate and then passed through a cottonfilter. Evaporation of the solvent afforded pure aniline in 98%yield.
91%	With sodium dihydrosulfite; potassium carbonate In dichloromethane; lithium hydroxide monohydrate at 35℃; for 5h;
91%	With ammonia hydrochloride; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate; zinc In lithium hydroxide monohydrate at 20℃; for 8h;
90%	With hydrogen In ethanol at 25℃; for 3h; Sealed tube; Green chemistry;
89%	With potassium fluoride; PMHS; palladium diacetate In tetrahydrofuran; lithium hydroxide monohydrate at 20℃; for 0.5h;
89%	With hydrogen In lithium hydroxide monohydrate at 25℃; for 15h; Green chemistry; chemoselective reaction;	2.3 Procedure for the nitroarene reduction by using Pt-BNP. General procedure: Nitroarene (0.5 mmol) and Pt-BNP 3 (9.8 mg, 2.5 mol%, 25 wt% of Pt by ICP-OES analysis) were taken in an oven dried reaction tube equipped with magnetic pellet. Water (2.0 mL)was added to the reaction tube and the resulting reaction mixture was stirred at room temperature under hydrogen atmosphere (using H2 balloon) and the reaction was monitored by TLC. After consumption of the starting material, crude product was extracted with ethyl acetate (3 × 20 mL). Then the organic phase was dried over Na2SO4 and concentrated in vacuum. The product was further purified by column chromatography using silica gel to yield pure aniline.
85%	With iron⁽⁰⁾; glacial acetic acid In ethanol; lithium hydroxide monohydrate at 30℃; for 1h; sonication;
85%	With hydrogenchloride; iron⁽⁰⁾ In ethanol; lithium hydroxide monohydrate for 1.5h; Reflux;
84%	With iron⁽⁰⁾; ammonia hydrochloride; glacial acetic acid In ethanol; lithium hydroxide monohydrate Reflux;
84%	With iron⁽⁰⁾; ammonia hydrochloride; glacial acetic acid In ethanol; lithium hydroxide monohydrate for 2.16667h; Reflux;
84.6%	With hydrogenchloride; iron⁽⁰⁾ In lithium hydroxide monohydrate Reflux;	3.S2 S2. Reduction reaction: In the reactor,Add 90g (1.6mol) iron powder and dilute hydrochloric acid (37.5% concentrated hydrochloric acid 95g mixed with 265g of water,Dilute hydrochloric acid mass fraction of 9.9%),Into the above solution, 49.5 g (0.3 mol) of 3-nitroacetophenone prepared from S1 was charged under vigorous stirring,Reflux mixing,After sufficient reaction to cool to room temperature,filter,The filtrate was adjusted to neutral with aqueous ammonia,filter,Washed,Dried to give 3-aminoacetophenone 34.3g, a yield of 84.6%The tested melting point of 97-99 ;
82%	With formic acid; tris(2-diphenylphosphinoethyl)phosphine In ethanol at 70℃; for 0.666667h;
81%	In N,N-dimethyl-formamide at 100℃; for 10h;
81%	With 1,3-DIOXOLANE; lithium hydroxide monohydrate; zinc at 70℃; for 11h; Green chemistry; chemoselective reaction;
81%	With anhydrous sodium formate In ethanol at 85℃; for 1h;
80%	With W-7 Raney-Nickel In ethanol for 5h; Heating;
80%	With ethanol; iron⁽⁰⁾; calcium(II) chloride In lithium hydroxide monohydrate at 60℃; for 0.5h; chemoselective reaction;
80%	With sodium tetrahydridoborate In lithium hydroxide monohydrate at 75℃; for 0.583333h;
77%	With molybdenum hexacarbonyl; 1,8-diazabicyclo[5.4.0]undec-7-ene In ethanol at 150℃; for 0.25h; microwave irradiation;
74%	With sodium tetrahydridoborate In lithium hydroxide monohydrate at 75℃; for 2.75h; Green chemistry;	2.4. The catalytic activity of PSeCN/Ag in the reduction of nitroarenes General procedure: Typically, 4-nitroaniline (1 mmol), NaBH4 as reducer (5 mmol), PSeCN/Ag nanocatalyst (20 mg) were added into a 10 mL vial containing 3 mL H2O as the solvent. Then, the reaction mixture was stirred for a certain time at 75 °C. The reaction was checked by TLC. Upon the completion of the reaction, the PSeCN/Ag was isolated by centrifugation and washed with EtOH and H2O to use for another consecutive run. Then, the product was extracted with ethyl acetate and purified by plate or column chromatography.
52%	Stage #1: 3-Nitroacetophenone In tetrahydrofuran at 20℃; for 24h; UV-irradiation; Stage #2: With aluminum(III) oxide In tetrahydrofuran for 18h; Reflux;
38%	Stage #1: 3-Nitroacetophenone With hydrogen bromide; hypophosphorous acid; glacial acetic acid; sodium iodide In lithium hydroxide monohydrate at 115℃; for 2h; Inert atmosphere; Stage #2: With sodium hydroxide In lithium hydroxide monohydrate Inert atmosphere;
	With palladium⁽⁰⁾; benzene Hydrogenation;
	With palladium on activated charcoal; ethanol; 2-methoxy-ethanol Hydrogenation;
	With palladium on activated charcoal; ethyl acetate Hydrogenation;
	With nickel; ethyl acetate Hydrogenation;
	With ethanol; platinum Hydrogenation;
	With ethanol; nickel at 50℃; Hydrogenation;
	With hydrogenchloride; stannous chloride
	With ammonium sulfide; ammonia
	With sodium dihydrosulfite
	With hydrogenchloride; tin
	With hydrogenchloride; ethanol; zinc
	With iron⁽⁰⁾; glacial acetic acid
	With ammonium sulfide
	With ammonia bei elektrolytischer Reduktion an Nickelkathoden;
	With hydrogenchloride; ethanol; stannous chloride
	With iron⁽⁰⁾; glacial acetic acid
	With ethanol; FERROUS SULFATE Reduktion;
	With anhydrous copper sulphate; sulfuric acid; copper(II) sulphate bei elektrolytischer Reduktion an Kupferkathoden;
	With ethanol; nickel at 50℃; Hydrogenation;
	With hydrogenchloride; triethylsilane; RhCl((C₆H₅)3P)3 1.) toluene, reflux, 2 h, 2.) methanol, room temperature, 2 h; Yield given. Multistep reaction;
	With morpholine; hydrogen In propan-2-one at 20℃;
	With hydrogenchloride; stannous chloride In ethanol; lithium hydroxide monohydrate at 30℃;
80 %Chromat.	With potassium hydroxide; isopropanol at 100℃; for 0.75h; Microwave irradiation; chemoselective reaction;
84 %Chromat.	With phenylsilane; triphenylphosphine; iron(II) dibromide In toluene at 110℃; for 16h; Inert atmosphere;
	Stage #1: 3-Nitroacetophenone With hydrogenchloride; tin In lithium hydroxide monohydrate Stage #2: With sodium hydroxide In lithium hydroxide monohydrate
95 %Chromat.	With hydrogen at 20℃; for 0.0833333h; Inert atmosphere; Neat (no solvent);
	With oxalic acid; titanium(IV) dioxide In lithium hydroxide monohydrate; acetonitrile at 24.84℃; for 1.5h; Inert atmosphere; UV-irradiation;
	With hydrogenchloride; dichloro-λ²-stannane dihydrate In methanol; lithium hydroxide monohydrate at 100℃;	9 Example 9 The reduction reaction of meta nitro acetophenone was carried out in a SS316 of 1/8" OD tube of volume 8.5 ml with 1 gm m-nitroacetophenone in 20 ml methanol and 5 gm SnCl2.2H20 in 20 ml 10% HC1 pumped using syringe pumps with a residence Time = 22 min at 100°C. The reaction was seen to be complete with only the product being observed at the outlet.
98 %Chromat.	With cadmium sulphide In isopropanol for 20h; Irradiation; Inert atmosphere;	2.3 Photocatalytic activity General procedure: The photocatalytic reduction of nitro compounds to their corresponding amines was performed using CdS nanopowder under visible blue LED irradiation. Typically, 20mg of the photocatalyst was added to the 5ml of 1×10-2M nitrocompounds solution in isopropanol. After that, the mixture was sunicated for 5min to obtain a homogeneous dispersion of CdS nanostructure in i-PrOH, then purged argon (5min) and then the vial was sealed up with a rubber stopper. The mixture was stirred magnetically during reaction (20h) and illuminated with a visible blue LED (3W) irradiation. After the reaction, for removing the photocatalyst particles completely, the mixture was centrifuged, and the remaining solution was analyzed with thin layer chromatography (TLC), and by Varian gas chromatograph (CP-3800). Conversion of nitro, yield of amine, and selectivity for amine were defined as follows: where C0 is the initial concentration of nitro compound and Cnitro and Camine are the concentration of the substrate nitro and the corresponding amine respectively, after the photocatalytic reaction.
100 %Chromat.	With titanium dioxide In ethanol for 0.75h; Irradiation; Green chemistry; chemoselective reaction;	Photocatalytic synthesis of aromatic amines General procedure: Photocatalytic synthesis of aromatic amines. Photocatalytic reactions were carried out in a round bottomed Pyrex flask and irradiated using four high power blue light LEDs 3W lamp or by solar light under magnetic stirring at room temperature. Reaction conditions with solar light: the reduction of the aromatic nitro compounds (0.02 mmol) was carried out in the presence of TiO2-P25 (0.01 g) in EtOH (4 mL) with irradiation for 1-4 h.
96 %Spectr.	With γ-terpinene In ethanol at 80℃; for 2h; Sealed tube; Green chemistry;
	With hydrogenchloride; dichloro-λ²-stannane dihydrate In methanol at 100℃; for 0.366667h;	2; 9 Reduction of m-Nitro Acetophenone Reduction of m-Nitro Acetophenone [0060] Continuous Flow Experiments: [0061] The reaction was carried out in a SS316 of ″ OD tube of volume 8.5 ml with 1 gm m-nitroacetophenone in 20 ml methanol and 5 gm SnCl2.2H2O in 20 ml 10% HCl pumped using syringe pumps with a residence Time=22 min at 100° C. The reaction was seen to be complete with only the product being observed at the outlet.
100 %Chromat.	With oxalic acid; titanium(IV) dioxide; β‐cyclodextrin In lithium hydroxide monohydrate for 1h; Inert atmosphere; Irradiation; Green chemistry;
	With oxalic acid; titanium(IV) dioxide In lithium hydroxide monohydrate; acetonitrile at 24.84℃; for 2h; Inert atmosphere; UV-irradiation; Sealed tube; chemoselective reaction;	4.1 General General procedure: Three kinds of commercial TiO2 samples were used as photocatalyst, i.e., P 25 (Degussa), ST-01 (Ishihara), and MT-150A (Tayca). Bare TiO2 powder (50mg) was suspended in a mixture of acetonitrile (Wako Pure Chemical Industries, Osaka) and water (5cm3) containing NS (50μmol, Sigma-Aldrich Japan, Tokyo) and oxalic acid (200μmol, Wako Pure Chemical Industries, Osaka) in a test tube. The tube was sealed with a rubber septum and then photoirradiated at a wavelength >300nm by a high-pressure mercury arc (Eiko-sha, 400W) under argon (Ar) with magnetic stirring at 298K. After the reaction, the gas phase was analyzed by a gas chromatograph (Shimadzu, GC-8A equipped with MS-5A columns). After the suspension had been filtered to remove the particles, the amounts of NS and product(s) were determined by high-performance liquid chromatography (Jasco, UV-2075Plus detector, PU-2089Plus pump, equipped with an Inertsil ODS-3 column, eluent: aqueous sodium borate buffer/acetonitrile=50:50, flow rate: 0.5cm3min-1 at room temperature) and GC-MS (GC-17A, GCMS-QP5050 (Shimadzu); column: DB-1, 0.25mm, 30m (J&W)).
	With hydrogen at 60℃; for 4h; Ionic liquid; chemoselective reaction;
	With β-D-glucopyranose; lithium hydroxide monohydrate at 25℃; for 12h; UV-irradiation;
93 %Chromat.	With hydrogen; triethylamine In tetrahydrofuran; lithium hydroxide monohydrate at 110℃; for 8h;
	With glacial acetic acid; zinc In lithium hydroxide monohydrate at 20℃;	General procedure General procedure: A mixture of nitrobenzenes 1 (1mmol) and Zn (215mg, 3.3mmol) in solvent of HOAc-H2O (2.5mL, v/v=2:3) in a flask was stirred at room temperature until the starting nitrobenzenes were consumed completely (monitored by TLC analysis). NaNO2 (1.1mmol) saturated solution was added dropwise at 0-5°C in an ice-water bath followed by adding a 1.5mmol of NaN3 saturated solution. Then the ice-water bath was removed and the reaction proceeded at room temperature. After 2h, terminal alkynes 2 (1.2mmol), CuI (0.05mmol) and DMSO (1.5mL) were added to the above system at room temperature. After 5h, the mixture was treated with H2O (15mL) and extracted with EtOAc (3×15mL) and the combined organic layer was washed with brine (3×5mL), dried over Na2SO4 and concentrated under reduced pressure to afford a crude product. Purification by column chromatography on silica gel afforded the desired 1,4-disubstitued 1,2,3-triazol 3.
	With ammsnium formate In lithium hydroxide monohydrate at 90℃; for 15h; Inert atmosphere; Green chemistry; chemoselective reaction;
99 %Chromat.	With cadmium sulphide In isopropanol for 0.75h; Inert atmosphere; Sonication; Irradiation;	Experimental General procedure: As optimized reaction conditions, a solution of nitroaromaticcompounds (0.01 M) in an appropriatesolvent and 20 mg of CdS-NP were sonicated andslowly purged with N2 for 5 min. Then, the reactionvessel was sealed up with a rubber stopper and themixture was stirred magnetically and irradiated with blue LED (4 × 1 W, λ ≥ 420 nm, intensity: 80 lumen)or sunlight (of daily ambient temperature andsunlight intensity range of 80-100 × 103 lux).The reaction conversion was monitored by thinlayer chromatography (TLC). After completing thereaction, the mixture was centrifuged and supernatantwas removed and analyzed on a GC Alientgas chromatograph (Nonpolar CP-Sil 8 column (30m × 0.32 mm), Varian Chrompack (Middelburg, TheNetherlands).
	With hydrogen In neat (no solvent) at 85℃; for 1.5h; Green chemistry;
100 %Chromat.	With hydrazine hydrate monohydrate at 85℃; for 6h; chemoselective reaction;
86 %Chromat.	With borane-ammonia complex In methanol; lithium hydroxide monohydrate at 20℃; for 2h; Sonication; chemoselective reaction;
86 %Chromat.	With formic acid In lithium hydroxide monohydrate; isopropanol at 20℃; for 3h; Irradiation; chemoselective reaction;
77 %Chromat.	With C₁₈H₁₃Cl₂N₃ORu; sodium isopropanolate; isopropanol at 110℃; for 5h; Inert atmosphere; Schlenk technique; chemoselective reaction;
	With formic acid; ammsnium formate In methanol at 25℃; for 1h;
> 99 %Chromat.	With borane-ammonia complex In methanol; lithium hydroxide monohydrate at 25℃; for 0.0833333h;
89 %Chromat.	With hydrogen In ethanol; lithium hydroxide monohydrate at 110℃; for 16h; Autoclave;	2.4 General methods for catalytic reactions in the autoclave General procedure: In an 8mL glass vial fitted with a magnetic stirring bar and a septum cap, the catalyst (the amount depends on the catalyst) was added followed by the nitroarene (0.5mmol), the internal standard (hexadecane, 20mg) and the solvent (2mL). A needle was inserted in the septum cap, which allows dihydrogen to enter. The vials (up to 7) were placed into a 300mL steel Parr autoclave which was flushed twice with dihydrogen at 20bar and then pressurized to 50bar. Then the autoclave was placed into an aluminum block pre-heated at 110°C. At the end of the reaction, the autoclave was quickly cooled down at room temperature with an ice bath and vented. Finally, the samples were removed from the autoclave, diluted with a suitable solvent, filtered using a Pasteur pipette filled with Celite (6cm pad) and analyzed by GC using n-hexadecane as an internal standard. Control experiments showed that the position of the vial inside the autoclave is not influential. The same outcome was obtained when the reaction was repeated by moving a vial from a peripheral to a central position.
96 %Chromat.	With sodium tetrahydridoborate In ethanol; lithium hydroxide monohydrate at 20℃; for 4h; Inert atmosphere;
	With formic acid In lithium hydroxide monohydrate at 25℃; for 0.75h;
	With hydrogen In tetrahydrofuran; lithium hydroxide monohydrate at 120℃; for 2h; chemoselective reaction;
	With formic acid; ammsnium formate In ethanol; lithium hydroxide monohydrate at 25℃; for 0.6h; chemoselective reaction;
100 %Chromat.	With cadmium sulfide loaded on silica-coated Fe₃O₄ nanoparticles In isopropanol for 20h; Irradiation; Inert atmosphere;	2.3 Photocatalytic activity General procedure: The Fe3O4/SiO2/CdS (S2) with average amount of CdS has been chosen as a photocatalyst for the photocatalytic reduction of nitro compounds under the blue LED irradiation. In a 10mL flask, 5ml of 0.01M nitro compounds solution and 0.02g photocatalyst were charged. Then the flask was charged with pure argon. The resulting mixture was stirred for 20h under LED irradiation. After this time, the catalyst was simply separated by employing an external magnetic field and the remaining solution was analyzed using thin-layered chromatography (TLC) and Varian gas chromatograph (CP-3800). The conversion of nitro substrate, yield of amine, and selectivity for amine were defined as follows: Conversion (%) = (C0-Cnitro)/C0×100 Yield (%) = Camine/C0×100 Selectivity (%) =Camine/(C0-Cnitro)×100Where C0 is the initial concentration of nitro compound and Cnitro and Camine are the concentration of the nitro substrate and the corresponding amine respectively, after the photocatalytic reaction.
99 %Spectr.	With C₂₂H₂₅Cl₂N₃ORuS₂; potassium hydroxide In isopropanol at 82℃; for 12h; chemoselective reaction;	2.4 Transfer hydrogenation of carbonyl/nitro compounds General procedure: Catalyst (0.1mol %) and KOH (1mmol) were dissolved in 2-propanol (4mL). To this solution, substrate (1mmol) was added and the mixture was refluxed (82°C). The progress of the reaction was monitored by GC at regular intervals. After the completion of the reaction, the reaction mixture was cooled to room temperature and filtered through silica gel or alumina bed, and eluted using 50% ethyl acetate-hexane mixture. The eluted solution was reduced and analyzed by GC and/or GCMS.
	With hydrogen In ethanol at 20℃; for 2h; chemoselective reaction;	Catalytic Experiment General procedure: In this work, the following of nitroaromatic compoundswere used:The liquid-phase hydrogenation reaction of nitroaromaticcompounds can be presented as:It was carried out at room temperature under an atmosphericpressure of H2. A sample of the catalyst(50 mg) was placed in a round-bottomed threeneckedflask and the system was purged with hydrogenfor 30 min. A solution of the substrate in ethanol 0.2 M(or in tetrahydrofuran in the case of using o- andp-dinitrobenzene as a substrate) was then poured intothe reactor by means of a feed cock of the reactionmixture. The concentration of platinum in the reactionmixture was 0.85 mol %. The reaction was carriedout with vigorous stirring on a magnetic stirrer at a rateof 900 rpm in the monitoring mode by means of gasliquidchromatography until the peak of the startingcompound disappeared on the chromatogram. At theend of the experiment, the stirring was stopped; thecatalyst was separated from the reaction mixture bycentrifugation.Analysis of the reaction products was performedusing GC with a Chromatek Crystal 5000.2 chromatographwith a flame ionization detector (FID) and acapillary column CR-5 (2 mm × 25 m) at a temperatureof 190°C. The peaks were identified on the basis of the experimentally obtained retention times of individualcompounds (nitrobenzene, o-dinitrobenzene,p-dinitrobenzene, p-hydroxynitrobenzene, p-nitroacetophenone,nitrocyclohexane, aniline, o-phenylenediamine,p-phenylenediamine, p-hydroxyaniline,p-nitrophenylethanol, aminocyclohexane). Thestructure and purity of the products obtained wereconfirmed by NMR spectroscopy. The 1H and 13CNMR spectra were recorded on a Bruker Avance 300spectrometer in solvents CDCl3 and DMSO-d6.
	With hydrogen In toluene at 30℃; Autoclave;	2.5. Catalytic hydrogenation of nitroarenes General procedure: The liquid-phase hydrogenation reaction of nitroarenes wasperformed in a magnetically stirred 50 mL stainless steel autoclave.A quantity of catalyst (50 mg) was added to the autoclavecontaining nitroarene (1 mmol) and toluene (15 mL). Then, theautoclave was flushed with 10 bar hydrogen five times. Afterbeing sealed, the autoclave was charged with H2 until 5 bar andthen it was kept at 30 °C. A rotation rate of 1000 r/min was used in this work, which can effectively exclude the influence ofmass transfer on the reactions. The reactants and productswere analyzed with a gas chromatograph (GC-112A, FID detector)equipped with an HP-5 column (30 m). In the recyclingexperiments, the solid catalyst was separated by simple decantationand directly used for the next cycle without any further treatment.

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8
[ 541-41-3 ]
[ 99-03-6 ]
[ 39569-24-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine In acetone for 3h; Reflux;	3.2.1. General Procedure For the Preparation of Alkyl (3-/4-Acetylphenyl)carbamates (3a-h) General procedure: Into a stirred solution of 3-aminoacetophenone 1a (CAS Registry Number 99-03-6; 5.00 g, 37 mmol)or 4-aminoacetophenone 1b (CAS Registry Number 99-92-3; 5.00 g, 37 mmol) and pyridine (3.0 mL,37 mmol) in 20 mL of acetone, a solution of methyl chloroformate 2a (CAS Registry Number 79-22-1;3.5 mL, 37 mmol), ethyl chloroformate 2b (CAS Registry Number 541-41-3; 4.0 mL, 37 mmol), propylchloroformate 2c (CAS Registry Number 109-61-5; 4.5 mL, 37 mmol) or butyl chloroformate 2d (CASRegistry Number 592-34-7; 5.0 mL, 37 mmol) in 5 mL of acetone, was added dropwise. The particularmixture was heated to reflux for 3 h [28]. When the reaction was completed (TLC control), the solventswere removed in vacuo, crude solid products 3a-h were washed with distilled water and recrystallizedfrom absolute ethanol. Full characterization data for the compounds 3a-h (Scheme 1), isolated ascolourless solids, are given below.
	In diethyl ether Ambient temperature;
	With N-ethyl-N,N-diisopropylamine In dichloromethane	11 [3-[3-(Dimethylamino)-1-oxo-2-propenyl]phenyl]methylcarbamic acid, ethyl ester EXAMPLE 11 [3-[3-(Dimethylamino)-1-oxo-2-propenyl]phenyl]methylcarbamic acid, ethyl ester A mixture of 27.03 g of m-aminoacetophenone, 27.14 g of diisopropylethylamine, 22.8 g of ethylchloroformate and 300 ml of dichloromethane was reacted as described in Example 1, giving 37.9 g of (3-acetylphenyl)carbamic acid, ethyl ester.

With potassium carbonate In chloroform at 0 - 20℃;

2.1 Typical procedure for the preparation of the ethyl phenylcarbamate General procedure: A solution of aniline (1.02 g, 1 ml, 11 mmol, 1 equiv.) in chloroform (15 ml) was cooled to 0°C in a flask equipped with a magnetic stirring bar, then ethyl chloroformate (1.43 g, 1.26 ml, 13.2 mmol, 1.2 equiv.) and K2CO3 (3.03 g, 22 mmol, 2 equiv.) were added while stirring. The reaction was slowly allowed to warm to room temperature and monitored by TLC until complete consumption of the aniline. After this time, the reaction mixture was cooled again to 0°C and quenched with 20 ml of water, before being diluted with CH2Cl2 and washed with 2N solution of HCl and brine. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product as a pale-yellow solid (1,34 g, 74% yield) was used without further purification.

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9
[ 99-03-6 ]
[ 124-63-0 ]
[ 2417-42-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine In dichloromethane at 20℃; for 3h;
59%	With triethylamine In dichloromethane at 0℃;
47.5%	Stage #1: 1-(3-aminophenyl)ethanone With triethylamine In dichloromethane at 20℃; for 0.166667h; Stage #2: methanesulfonyl chloride In dichloromethane at 20℃; for 24h;	63.1 [Step 1] N-(3-acetylphenyl)methanesulfonamide Triethylamine (1.333 mL, 9.618 mmol) was added to a solution of 1-(3-aminophenyl)ethan-1-one (1.000 g, 7.398 mmol) in dichloromethane (14 mL) at the room temperature, and the mixture was stirred at the same temperature for 10 mm. The reaction mixture was treated with methanesulfonyl chloride (0.630 mL, 8.139mmol), and stirred for additional 24 hr at the same temperature. Then, water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (Si02, 24 g cartridge; ethyl acetate / hexane = 0 % to 30 %) to give N(3-acetylphenyl)methanesulfonamide as white solid (0.750 g, 47.5 %).

	With pyridine
	With pyridine

Reference： [1]Lauria, Antonino; Abbate, Ilenia; Gentile, Carla; Angileri, Francesca; Martorana, Annamaria; Almerico, Anna Maria [Journal of Medicinal Chemistry, 2013, vol. 56, # 8, p. 3424 - 3428]
[2]Location in patent: experimental part Lovering, Frank; Kirincich, Steve; Wang, Weiheng; Combs, Kerry; Resnick, Lynn; Sabalski, Joan E.; Butera, John; Liu, Julie; Parris, Kevin; Telliez [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 9, p. 3342 - 3351]
[3]Current Patent Assignee: CHONGKUNDANG HOLDINGS CORP. - WO2017/18803, 2017, A1 Location in patent: Paragraph 1008; 1009; 1010
[4]Uloth; Kirk; Gould; Larsen [Journal of medicinal chemistry, 1966, vol. 9, # 1, p. 88 - 97]
[5]Laurence, C.; Berthelot, M.; Lucon, M.; Tsuno, Y. [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 1982, vol. 38, # 7, p. 791 - 796]
[6]Zhang, Yu-Juan; Shen, Liu-Lan; Cheon, Hyae-Gyeong; Xu, Yong-Nan; Jeong, Jin-Hyun [Archives of Pharmacal Research, 2014, vol. 37, # 5, p. 588 - 599]

10
[ 99-03-6 ]
[ 79-19-6 ]
[ 87743-92-8 ]

Yield	Reaction Conditions	Operation in experiment
88.7%	In diethyl ether; acetic acid for 3h; Heating;
69%	With acetic acid In ethanol at 50 - 80℃; for 3h;	4.2.1 General procedure for the synthesis of 3-4 General procedure: To the solution of appropriate aminoacetophenones (5 mmol) in anhydrous ethanol (30mL), thiosemicarbazide (5 mmol) and acetic acid (0.5 mL) were added. The reaction mixture was stirred at 50-80 °C for 3 h and then cooled to room temperature. The precipitate solid was filtered and washed with ethanol to afford pure target compounds 3-4.
	With acetic acid In ethanol Ambient temperature;

With acetic acid In ethanol at 20℃; for 24h;

4.2.1 Preparation of thiosemicarbazones General procedure: A mixture of 0.01mol of appropriate acetophenone and 0.01mol of thiosemicarbazide in 25mL of ethanol was acidified with 2mL of acetic acid to pH 3-4 and maintained at room temperature for 24h. The solvent was evaporated under reduced pressure and the residue was washed with a warm saturated sodium bicarbonate solution to eliminate the start material and recrystallized from methanol. Mean yield of approximately 90%.

Reference： [1]Witek, Stanislaw; Bielawski, Jacek; Bielawska, Alicja [Polish Journal of Chemistry, 1981, vol. 55, # 12, p. 2589 - 2600]
[2]You, Ao; Zhou, Jie; Song, Senchuan; Zhu, Guoxun; Song, Huacan; Yi, Wei [European Journal of Medicinal Chemistry, 2015, vol. 93, p. 255 - 262]
[3]Pandeya; Aggarwal; Jain [Pharmazie, 1999, vol. 54, # 4, p. 300 - 302]
[4]Blau, Lorena; Menegon, Renato Farina; Trossini, Gustavo H. G.; Molino, João Vitor Dutra; Vital, Drielli Gomes; Cicarelli, Regina Maria Barretto; Passerini, Gabriela Duó; Bosquesi, Priscila Longhin; Chin, Chung Man [European Journal of Medicinal Chemistry, 2013, vol. 67, p. 142 - 151]

11
[ 99-03-6 ]
[ 407-25-0 ]
[ 56915-87-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine In dichloromethane at 0℃; for 0.5h;	15 Example 15: General procedure for the preparation of N- methyl-enamine-sulfonamides of general formula (VII) following Scheme 4 N- (3-ACETYLPHENYL)-2, 2,2-trifluoroacetamide 5 g (37 mmol) of 3-aminoacetophenone were dissolved in 30 ml of anhydrous dichloromethane. To the resultant solution 3.15 ml (38.84 mmol) of anhydrous pyridine and 5.5 ml (38.84 mmol) of trifluoroacetic anhydride were added at 0°C. The reaction mixture was stirred for 30 minutes at the same temperature and poured onto 100 ml of water-ice. 100 ml of a saturated solution of sodium chloride were added and extracted with 2X70 ml of dichloromethane and 3X50 ml of ethyl acetate. The organic layers were washed with water, dried over anhydrous sodium sulfate and evaporated to dryness by reduced pressure distillation. 8. 7 g (yield= 100%) as a solid of N- (3-ACETYLPHENYL)-2, 2,2- trifluoroacetamide were obtained.
80%	In N,N-dimethyl-formamide for 48h; Ambient temperature;
	With trifluoroacetic acid Heating;

4.03 g

With pyridine In dichloromethane at 20℃; Cooling with ice;

6 Synthesis of intermediate C6-2: Dissolve C6-1 (2.5g, 18.5mmol) and pyridine (1.6mL) in dichloromethane (15mL),Add trifluoroacetic anhydride (4.08g, 19.42mmol) dropwise under ice bath,It was naturally warmed to room temperature and stirred overnight. The reaction solution was added to water, extracted with dichloromethane, dried and concentrated, and column chromatography was used to obtain 4.03 g of compound C6-2.

Reference： [1]Current Patent Assignee: FERRER INTERNACIONAL SA - WO2005/14597, 2005, A1 Location in patent: Page/Page column 47; 48
[2]Vigorita; Previtera; Saporito; Costa De Pasquale; Circosta; Occhiuto [Farmaco, Edizione Scientifica, 1984, vol. 39, # 5, p. 403 - 413]
[3]Zhang; Haemers; Vanden Berghe; Pattyn; Bollaert; Levshin [Journal of Heterocyclic Chemistry, 1991, vol. 28, # 3, p. 673 - 683]
[4]Current Patent Assignee: FERRER INTERNACIONAL SA - WO2006/84835, 2006, A1 Location in patent: Page/Page column 7
[5]Current Patent Assignee: ZHEJIANG TONGYUANKANG MEDICINE; TYK MEDICINES - CN113045569, 2021, A Location in patent: Paragraph 0294-0298

12
[ 99-03-6 ]
[ 67500-19-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1509 - 1520

13
[ 99-03-6 ]
[ 35203-88-4 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1982,vol. 30,p. 4092 - 4101

14
[ 99-03-6 ]
[ 2454-37-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 1-(3-aminophenyl)ethanone With [(N,N'-bis(diisopropylphosphino)-2,6-diaminopyridine)Mn(CO)₂H] In 1,2-dimethoxyethane at 110℃; for 18h; Inert atmosphere; Sealed tube; Stage #2: With sodium hydroxide at 25℃; for 18h; Inert atmosphere;	General procedure for hydrosilylation reactions General procedure: Inside an Ar-flushed glovebox, an 8 cm3 microwave vial was charged with complex (0.01-0.03 mol%), carbonyl substrate (0.35 mmol), 2 cm3 solvent, and silane (0.035-0.1 mmol) in this order. A stirring bar was added, and the vial was sealed. The closed vial was removed from the glovebox and stirred for 18 h at the indicated temperature in a heated aluminum block. The vial was allowed to reach room temperature and the reaction was quenched by exposure to air. In case of screening reactions, fluorobenzene (0.35 mmol) was added and the reaction mixture was analyzed by 19F{1H} NMR. Isolation of the product To the reaction mixture 2 cm3 of a 20 wt% NaOH-solution were added and the solution was stirred for 18 h at room temperature. The phases were separated, and the aqueous phase was three times extracted with 2 cm3 diethyl ether. The combined organic phases were filtrated over a pad of silica, dried over Na2SO4 and the solvent was removed. Spectroscopic data of all isolated products are in line with the literature [11, 42-49].
86%	Stage #1: 1-(3-aminophenyl)ethanone With C₃₆H₃₆FeN₆ at 50℃; for 4.5h; Inert atmosphere; Glovebox; Stage #2: With water; sodium hydroxide at 50℃; for 1.5h;
86%	With methanol; sodium tetrahydroborate at 20℃; for 1.5h; Sealed tube; Inert atmosphere;

84%	Stage #1: 1-(3-aminophenyl)ethanone With sodium tetrahydroborate In ethanol at 0℃; for 3h; Stage #2: With hydrogenchloride In ethanol; water	38.1 Synthesis of 8-[1-(Dimethylamino)ethyl]-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-5(6H)-one dihydrochloride Step 1: Synthesis of 1-(3-aminophenyl)ethanol [Show Image] 3-aminoacetophenon (2.0 g, 14.80 mmol) was dissolved in ethanol (25 ml) and added with sodium borohydride (1.4 g, 36.99 mmol) at 0 °C. The resulting mixture was stirred for 3 hours and poured into ice water. The mixture was neutralized with 2 N hydrochloric acid acqueous solution and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (1.7 g, yield:84%, white solid). 1H NMR(400MHz, CDCl3); δ 7.13(t, J=8.0Hz, 1H), 6.76-6.72(m, 2H), 6.60(dd, J=8.0Hz, 2.4Hz, 1H), 4.81(m, 1H), 1.46(d, J=6.8Hz, 3H)
84%	Stage #1: 1-(3-aminophenyl)ethanone With sodium tetrahydroborate In ethanol at 0℃; for 3h; Stage #2: With water In ethanol	38.1 Step 1: Synthesis of 1-(3-aminophenyl)ethanol 3-aminoacetophenon (2.0 g, 14.80 mmol) was dissolved in ethanol (25 ml) and added with sodium borohydride (1.4 g, 36.99 mmol) at 0° C. The resulting mixture was stirred for 3 hours and poured into ice water. The mixture was neutralized with 2 N hydrochloric acid aqueous solution and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (1.7 g, yield:84%, white solid). 1H NMR(400 MHz, CDCl3); δ 7.13(t, J=8.0 Hz, 1H), 6.76-6.72(m, 2H), 6.60(dd, J=8.0 Hz, 2.4 Hz, 1H), 4.81(m, 1H), 1.46(d, J=6.8 Hz, 3H)
81%	With chloro(1,5-cyclooctadiene)rhodium(I) dimer; potassium trifluoroacetate; diphenyl(methyl)phosphine; bis(pinacol)diborane In tetrahydrofuran; cyclohexane at 20℃; for 24h; regioselective reaction;
76%	With [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; sodium formate In water at 30℃; for 24h; Inert atmosphere; Schlenk technique; enantioselective reaction;	2.3. General procedure for the catalytic reductions General procedure: In a schlenk tube, the chiral ligand (0.05 mmol) and the metallicprecursor (0.025 mmol) are dissolved in the water (4 mL). After 1 hof stirring at 30 °C, the sodium formate (10 mmol) and the ketone (1 mmol) were added to the aqueous solution. The biphasic solution was stirred at 30 for the indicated time and follow by TLC untilthe total reduction of ketone. The formed alcohol was separated from the catalyst by simple extraction with pentane (2 8 mL) and the organic layer was dried over MgSO4 and concentrated in vacuo.The crude residue was distilled in order to purify the alcohol.
72%	With potassium hydroxide In isopropyl alcohol at 82.84℃; for 3h;
67%	With CpRu(PiPr₃)(CH₃CN)2PF₆; potassium <i>tert</i>-butylate In isopropyl alcohol at 20℃; for 3h;
10%	With glucose dehydrogenase; D-glucose; ketoreductase from Pichia glucozyma; nicotinamide adenine dinucleotide phosphate In aq. buffer at 30℃; Enzymatic reaction; enantioselective reaction;
36 % Spectr.	With sodium tetrahydroborate; acetic acid at 16 - 21℃; for 0.166667h;
99 % Spectr.	With sodium isopropylate In isopropyl alcohol at 82℃; for 48h;
68 % Chromat.	With potassium hydroxide; isopropyl alcohol at 82.84℃; for 3h;
	With Candida tenuis AKR₂B₅ xylose reductase [E_.⁽¹⁾C₁₁₁₇₅]; water; NADH In ethanol at 25℃; aq. phosphate buffer; Enzymatic reaction;
	Multi-step reaction with 2 steps 1: C₂₄H₅₀FeO₂P₄ / toluene / 48 h / 80 °C / Inert atmosphere 2: water; sodium hydroxide / methanol; toluene / 48 h / 50 °C
	With sodium tetrahydroborate In methanol
	With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 9h; Inert atmosphere; Schlenk technique; Glovebox; chemoselective reaction;
	With methanol; sodium tetrahydroborate at 0℃; for 1h;
	With methanol; sodium tetrahydroborate Inert atmosphere;
34 %Chromat.	With hydrogen In methanol at 80℃; for 1h; Autoclave;
88 %Chromat.	With hydrogen In water at 80℃; for 1h; Autoclave;

Reference： [1]Weber, Stefan; Iebed, Dina; Glatz, Mathias; Kirchner, Karl [Monatshefte fur Chemie, 2021, vol. 152, # 6, p. 635 - 639]
[2]Liang, Qiuming; Liu, Nina Jiabao; Song, Datong [Dalton Transactions, 2018, vol. 47, # 29, p. 9889 - 9896]
[3]Nelson, Hope; Richard, William; Brown, Hailee; Medlin, Abigail; Light, Christina; Heller, Stephen T. [Angewandte Chemie - International Edition, 2021, vol. 60, # 42, p. 22818 - 22825][Angew. Chem., 2021, vol. 133, # 42, p. 23000 - 23007]
[4]Current Patent Assignee: JEIL PHARMA HOLDINGS INC - EP2364983, 2011, A2 Location in patent: Page/Page column 53
[5]Current Patent Assignee: JEIL PHARMA HOLDINGS INC - US2011/218193, 2011, A1 Location in patent: Page/Page column 43
[6]Zhang, Bing; Xu, Xin; Tao, Lei; Lin, Zhenyang; Zhao, Wanxiang [ACS Catalysis, 2021, vol. 11, # 15, p. 9495 - 9505]
[7]Boukachabia, Mourad; Aribi-Zouioueche, Louisa; Riant, Olivier [Journal of Organometallic Chemistry, 2018, vol. 868, p. 95 - 101]
[8]Selvam, Parasuraman; Mohapatra, Susanta K.; Sonavane, Sachin U.; Jayaram, Radha V. [Tetrahedron Letters, 2004, vol. 45, # 9, p. 2003 - 2007]
[9]Lee, Sun-Hwa; Nikonov, Georgii I. [ChemCatChem, 2015, vol. 7, # 1, p. 107 - 113]
[10]Contente, Martina L.; Serra, Immacolata; Palazzolo, Luca; Parravicini, Chiara; Gianazza, Elisabetta; Eberini, Ivano; Pinto, Andrea; Guidi, Benedetta; Molinari, Francesco; Romano, Diego [Organic and Biomolecular Chemistry, 2016, vol. 14, # 13, p. 3404 - 3408]
[11]Nieminen, Tuula, E. A.; Hase, Tapio A. [Tetrahedron Letters, 1987, vol. 28, # 40, p. 4725 - 4728]
[12]Standfest-Hauser; Slugovc; Mereiter; Schmid; Kirchner; Xiaoc; Weissensteiner [Journal of the Chemical Society, Dalton Transactions, 2001, # 20, p. 2989 - 2995]
[13]Mohapatra, Susanta K.; Sonavane, Sachin U.; Jayaram, Radha V.; Selvam, Parasuraman [Organic Letters, 2002, vol. 4, # 24, p. 4297 - 4300]
[14]Location in patent: experimental part Vogl, Michael; Kratzer, Regina; Nidetzky, Bernd; Brecker, Lothar [Organic and Biomolecular Chemistry, 2011, vol. 9, # 16, p. 5863 - 5870]
[15]Bhattacharya, Papri; Krause, Jeanette A.; Guan, Hairong [Organometallics, 2011, vol. 30, # 17, p. 4720 - 4729]
[16]Ferreira, Daniele Alves; Da Costa Assunção, João Carlos; De Lemos, Telma Leda Gomes; Monte, Francisco José Queiroz [Biocatalysis and Biotransformation, 2012, vol. 30, # 5-6, p. 469 - 475]
[17]Revunova, Kseniya; Nikonov, Georgii I. [Chemistry - A European Journal, 2014, vol. 20, # 3, p. 839 - 845]
[18]Alsafadi, Diya; Alsalman, Safaa; Paradisi, Francesca [Organic and Biomolecular Chemistry, 2017, vol. 15, # 43, p. 9169 - 9175]
[19]Cai, Sheng; Shao, Nana; Chen, Yuanyuan; Li, Anbang; Pan, Jie; Zhu, Huajian; Zou, Hongbin; Zeng, Su; Sun, Lianli; Zhao, Jinhao [Organic Letters, 2019, vol. 21, # 12, p. 4411 - 4414]
[20]Bereta, Tomasz; Mieczyńska, Ewa; Ronka, Sylwia; Tylus, Włodzimierz; Trzeciak, Anna M. [New Journal of Chemistry, 2021, vol. 45, # 11, p. 5023 - 5028]
[21]Alsalahi, W.; Trzeciak, A. M.; Tylus, W. [Dalton Transactions, 2021, vol. 50, # 30, p. 10386 - 10393]

15
[ 99-03-6 ]
[ 6011-18-3 ]

Yield	Reaction Conditions	Operation in experiment
76.3%	With sodium hydroxide; hydroxylamine sulfate In diethyl ether for 3h; Heating;
68%	With hydroxylamine hydrochloride; sodium hydroxide In methanol at 20℃; Green chemistry;
68.2%	With hydroxylamine hydrochloride; sodium acetate trihydrate In ethanol at 55℃; for 12h;	Preparation of N,N'-phenyl-3-acetyl oxime -2,2'-(ethy-lenedioxy)bisbenzaldehyde (H2L4): 3-Aminoacetophenoneoxime was synthesized analogously to the method reported inthe previous literature. To a hot ethanolic solution (7 mL) of 3-aminoacetophenone (818.2 mg, 6 mmol) was added a mixed ethanolic solution (15 mL) of hydroxylamine hydrochloride (423.5 mg, 6 mmol) and sodium acetate trihydrate (480.4 mg,10 mmol), the colour of the mixing solution turned to pale-yellow. The mixture was stirred at 55 °C for 12 h. After cooling to room temperature, the mixture was filtered, washed succe-ssively with ethanol and n-hexane, respectively. The product was dried under reduced pressure to obtained brown needle-like solid. Yield, 68.2 %. m.p. 408-409 K. Anal. Calcd. for C8H10N2O (%): C, 63.98; H, 6.71; N, 18.65; Found: C, 63.91; H, 6.74; N, 18.62.

	With sodium hydroxide; hydroxylamine hydrochloride In ethanol; water
	With hydroxylamine hydrochloride; triethylamine In ethanol at 120℃; for 0.333333h; Microwave irradiation;
	With hydroxylamine hydrochloride; sodium acetate In methanol; water at 120℃; for 2h;

Reference： [1]Witek, Stanislaw; Bielawski, Jacek; Bielawska, Alicja [Polish Journal of Chemistry, 1981, vol. 55, # 12, p. 2589 - 2600]
[2]Aakeroey, Christer B.; Sinha, Abhijeet S. [RSC Advances, 2013, vol. 3, # 22, p. 8168 - 8171]
[3]Wang, Li; Gao, Su-Xia; Zhang, Yang; Li, Gang; Zhang, Yu-Jie [Asian Journal of Chemistry, 2014, vol. 26, # 18, p. 6272 - 6274]
[4]Location in patent: scheme or table Mazik, Monika; Buthe, Arno C. [Organic and Biomolecular Chemistry, 2008, vol. 6, # 9, p. 1558 - 1568]
[5]Location in patent: experimental part Lovering, Frank; Kirincich, Steve; Wang, Weiheng; Combs, Kerry; Resnick, Lynn; Sabalski, Joan E.; Butera, John; Liu, Julie; Parris, Kevin; Telliez [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 9, p. 3342 - 3351]
[6]Xiao, Fuhong; Yuan, Shanshan; Huang, Huawen; Zhang, Feng; Deng, Guo-Jun [Organic Letters, 2019, vol. 21, # 21, p. 8533 - 8536]

16
[ 99-03-6 ]
[ 70334-60-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With tert.-butylnitrite; trimethylsilylazide In acetonitrile at 0 - 20℃; for 2h; Inert atmosphere;
92%	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite In water; ethyl acetate at 0℃; for 1.25h; Stage #2: With sodium azide In water; ethyl acetate at 0 - 20℃; for 3h;
83%	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite at 0℃; Stage #2: With sodium azide at 0℃;

73%	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite at 0℃; Stage #2: With sodium azide
57%	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite In water Stage #2: With sodium azide In water
	With sodium azide; sulfuric acid; sodium nitrite 1) acetic acid, water, 0-5 deg C, 2 h; 2) acetic acid, water, 0-5 deg C, 1 h; Yield given. Multistep reaction;
	With sodium azide; sodium nitrite Acidic conditions;
	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite In water Stage #2: With sodium azide In water
	Stage #1: 1-(3-aminophenyl)ethanone With acetic acid; sodium nitrite In water at 0 - 5℃; Stage #2: With sodium azide In water; acetic acid at 0 - 20℃; for 2h;	General procedure General procedure: A mixture of nitrobenzenes 1 (1mmol) and Zn (215mg, 3.3mmol) in solvent of HOAc-H2O (2.5mL, v/v=2:3) in a flask was stirred at room temperature until the starting nitrobenzenes were consumed completely (monitored by TLC analysis). NaNO2 (1.1mmol) saturated solution was added dropwise at 0-5°C in an ice-water bath followed by adding a 1.5mmol of NaN3 saturated solution. Then the ice-water bath was removed and the reaction proceeded at room temperature. After 2h, terminal alkynes 2 (1.2mmol), CuI (0.05mmol) and DMSO (1.5mL) were added to the above system at room temperature. After 5h, the mixture was treated with H2O (15mL) and extracted with EtOAc (3×15mL) and the combined organic layer was washed with brine (3×5mL), dried over Na2SO4 and concentrated under reduced pressure to afford a crude product. Purification by column chromatography on silica gel afforded the desired 1,4-disubstitued 1,2,3-triazol 3.
	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride In water at 0℃; Schlenk technique; Inert atmosphere; Stage #2: With sodium nitrite In water at 0 - 5℃; for 0.166667h; Schlenk technique; Inert atmosphere; Stage #3: With sodium azide In water at 0 - 20℃; Schlenk technique; Inert atmosphere;
	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; acetic acid; sodium nitrite In water at 0℃; for 0.5h; Stage #2: With sodium azide In water at 0 - 20℃;
	With hydrogenchloride; sodium azide; sodium nitrite In hexane; water	8.A Step A: Step A: Preparation of 3-acetylphenylazide A mixture of 10.8g. (0.08 mole) of 3-acetylaniline in 50 ml. of water was treated with 20 ml. of concentrated HCl and cooled to 0° C. There was then added a solution of 6.07g. (0.088 mole) of NaNO2 in 20 ml. of water. The reaction mixture was aged for 20 minutes, and there was then added 25 ml. of hexane and 25 ml. of ether, followed by a solution fo 5.72g. (0.088 mole) of NaN3 in 20 ml. of water. The reaction mixture was aged for 1/2 hour at room temperature, after which the aqueous and organic components were separated, and the aqueous component extracted with 50 ml. of ether. The organic component and extract were dried over MgSO4 and concentrated under reduced pressure to 12.72g. (99%) of product whose structure as 3-acetylphenylazide was confirmed by IR.
	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite In water at 0℃; for 0.166667h; Stage #2: With sodium azide In water at 20℃; for 2h;	Synthesis of compound 2 A 100-mL round-bottom flask was charged with a hydrochloric acid solution (3.2 mL, 6 M), and 3-aminoacetophenone (676 mg, 5 mmol) was added. This mixture was cooled to 0 °C with an ice bath, and a solution of NaNO2 (350 mg, 5.13 mmol) in H2O(1.8 mL) was added. The reaction mixture was stirred for 10 min, and a solution of NaN3(330 mg, 5.1 mmol) in H2O (1.8 mL) was added dropwise.The ice bath was removed, and the reaction mixture was stirred at ambient temperature for 2 h. Diethyl ether (10 mL × 3) was added, and the organic phase was dried in vacuo affording the azide intermediate as a dark brown liquid. To the flask charged with organic azide, 1-hexyne (555μL, 5 mmol), complex [CuCl(IPr)] as the precatalyst (25 mg,0.05 mmol), MeOH (2 mL) and H2O(1 mL) were successively added. The reaction mixture was stirred and heated at 60 °C for 24 h. After cooling down to ambient temperature,the resulting precipitate was collected and dried in vacuo affording the product as a dark brown liquid 2 (1.024 g,3.2 mmol, 95%)

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[11]Kapkoti, Deepak Singh; Singh, Shilpi; Luqman, Suaib; Bhakuni, Rajendra Singh [New Journal of Chemistry, 2018, vol. 42, # 8, p. 5978 - 5995]
[12]Current Patent Assignee: MERCK & CO INC - US4145364, 1979, A
[13]Zhang, Xin; Yan, Xuechao; Zhang, Bo; Wang, Ran; Guo, Shuai; Peng, Shiyong [Transition Metal Chemistry, 2019, vol. 44, # 1, p. 39 - 48]

17
[ 99-03-6 ]
[ 104408-23-3 ]
3-{1-[(3,5-dichloro-pyridin-2-yl)-hydrazono]-ethyl}-phenylamine [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,2000,vol. 36,p. 931 - 943

18
[ 99-03-6 ]
[ 214470-55-0 ]
4-(3-acetylphenylamino)-6,7-dimethoxy-3-quinolinecarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		4-(3-Acetylphenylamino)-6,7-dimethoxy-3-quinolinecarbonitrile In the manner of Example 274 reaction of <strong>[214470-55-0]4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile</strong> with 3-aminoacetophenone gave the title compound as a tan solid, mp 204-206 C.
		4(3-acetylphenylamino)-6,7-dimethoxy-3-quinolinecarbonitrile In the manner of Example 274 reaction of <strong>[214470-55-0]4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile</strong> with 3-aminoacetophenone gave the tide compound as a tan solid, mp 204-206 C.
		Example 324 4-(3-acetylphenylamino)-6,7-dimethoxy-3-quinolinecarbonitrile In the manner of Example 274 reaction of <strong>[214470-55-0]4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile</strong> with 3-aminoacetophenone gave the title compound as a tan solid, mp 204-206C.

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3244 - 3256
[2]Patent: US6384051,2002,B1
[3]Patent: US6002008,1999,A
[4]Patent: EP1263503,2005,B1

19
[ 99-03-6 ]
[ 105333-30-0 ]

Yield	Reaction Conditions	Operation in experiment
55%	With potassium peroxomonosulfate In dichloromethane; water monomer at 25℃; for 1h;	3; 9; 16 Synthesis of 3-nitrosoacetophenone First place 1.35g m-aminoacetophenone (10mmol) in a 100mL eggplant-shaped bottle, add 30mL of methylene chloride to dissolve, stir at room temperature (25 ); weigh 6.15g potassium peroxymonosulfonate Oxone (10mmol) An aqueous solution (30 mL) was gradually added dropwise to the reaction bottle. After the addition was completed, the reaction was continued to stir for one hour at room temperature.After the reaction, the reaction solution was extracted with methylene chloride of the organic phase, the organic phases were combined, dried over anhydrous sodium sulfate, and filtered with suction. The filtrate was spin-dried with an appropriate amount of silica gel, column chromatography, petroleum ether: ethyl acetate = 10:1 ( v: v) Elution.Spin dry to get a green solid.The yield is 55%.
	With H₂SO₆
	With potassium peroxymonosulfate In dichloromethane; water monomer at 20℃; for 4h;

With potassium peroxymonosulfate In dichloromethane; water monomer at 20℃; for 1.5h;

Reference： [1]Current Patent Assignee: EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN111217722, 2020, A Location in patent: Paragraph 0087-0088; 0089-0090; 0145-0148; 0201-0204
[2]Badjic; Kostic [Journal of Materials Chemistry, 2001, vol. 11, # 2, p. 408 - 418]
[3]Teders, Michael; Pogodaev, Aleksandr A.; Bojanov, Glenn; Huck, Wilhelm T. S. [Journal of the American Chemical Society, 2021, vol. 143, # 15, p. 5709 - 5716]
[4]Kobauri, Piermichele; Galenkamp, Nicole S.; Schulte, Albert M.; De Vries, Jisk; Simeth, Nadja A.; Maglia, Giovanni; Thallmair, Sebastian; Kolarski, Dušan; Szymanski, Wiktor; Feringa, Ben L. [Journal of Medicinal Chemistry, 2022, vol. 65, # 6, p. 4798 - 4817]

20
[ 94066-64-5 ]
[ 99-03-6 ]

Yield	Reaction Conditions	Operation in experiment
93%	With zinc; hydrazinium monoformate In methanol for 0.1h; Heating;
91%	With ammonium formate; magnesium In methanol at 20℃; for 0.15h;
91%	With ammonium chloride; zinc In methanol at 20℃; for 0.2h;

91%	With zinc In methanol at 25℃; for 0.25h; Inert atmosphere;
90%	With formic acid; zinc In methanol at 20℃; for 0.15h;
90%	With ammonium formate; nickel In methanol at 20℃; for 0.15h;
90%	With ammonium acetate; zinc In methanol at 20℃; for 0.0666667h;
90%	With magnesium In methanol at 25℃; for 0.3h; Inert atmosphere;	General Procedure for the Reduction of Azo Compounds General procedure: The experimental procedure for our reduction of azo compounds using CSF and magnesium is very simple. To a flame-dried flask equipped with a magnetic stirrer and condenser, the suspension of appropriate azo compound (5 mmol) in methanol (15 mL), CSF (1 g), and magnesium (5 mmol) were added and stirred under a nitrogen atmosphere at room temperature. Progress of the reaction was monitored by TLC until the starting material was consumed completely. Then the catalyst and resin were removed by filtration, and the solvent was evaporated under vacuum. All of the products were puried by silica-gel chromatography eluted with PE-EtOAc 5:1 and characterized by comparison of their TLC, melting points, IR spectra, 1H NMR , and 13C NMR spectra.
82%	With perchloric acid In isopropyl alcohol; acetonitrile at 25℃; for 0.666667h; Inert atmosphere; Irradiation;

Reference： [1]Gowda, Shankare; Abiraj; Gowda, D. Channe [Journal of Chemical Research - Part S, 2002, # 8, p. 384 - 385]
[2]Abiraj; Gowda, Shankare; Gowda, D. Channe [Journal of Chemical Research - Part S, 2003, # 5, p. 299 - 300]
[3]Sridhara; Srinivasa; Gowda, D. Channe [Synthetic Communications, 2004, vol. 34, # 8, p. 1441 - 1446]
[4]Han; Yu; Xu; Song; Yan; Ma; Zhen [Journal of Chemical Research, 2013, vol. 37, # 1, p. 55 - 56]
[5]Gowda, Shankare; Abiraj; Gowda, D.Channe [Tetrahedron Letters, 2002, vol. 43, # 7, p. 1329 - 1331]
[6]Gowda, D. Channe; Gowda, Shankare; Abiraj [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2003, vol. 42, # 7, p. 1774 - 1776]
[7]Srinivasa; Abiraj; Gowda, D. Channe [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 1, p. 192 - 195]
[8]Yu; Ma; Jin; Zhen [Synthetic Communications, 2014, vol. 44, # 5, p. 707 - 713]
[9]Location in patent: experimental part Farhadi, Saeid; Sepahvand, Shahnaz [Journal of Molecular Catalysis A: Chemical, 2010, vol. 318, # 1-2, p. 75 - 84]

21
[ 99-03-6 ]
[ 98-88-4 ]
[ 84833-25-0 ]

Yield	Reaction Conditions	Operation in experiment
96%
94.6%	With triethylamine In ethyl acetate at 25℃; for 6h;
92%	With triethylamine In ethyl acetate at 0 - 20℃; for 8h;

83%	With triethylamine In dichloromethane at 0 - 20℃; for 5h;	4.1.4 N-(3-acetylphenyl)benzamide (1d) A solvent of benzoyl chloride (7.2mmol, 1.0g) in DCM (10mL) was dropwise added to the mixture of 1-(2-aminophenyl)ethan-1-one (6mmol, 0.81g) and triethylamine (7.2mmol, 0.72g) in DCM (10mL) at 0°C and stirred for another 5hat room temperature. Then, the mixture was poured into ice water and the pH value was adjusted to 2.0 with hydrochloric acid (2M) and extracted with DCM. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was recrystallized from ethanol to give 1d (1.2g, 83%) as a white solid. 1H NMR (400MHz, DMSO-d6) δ 10.46 (s, 1H), 8.39 (s, 1H), 8.09 (d, J=8.0Hz, 1H), 8.00 (d, J=7.8Hz, 2H), 7.73 (d, J=7.6Hz, 1H), 7.56 (td, J=19.7, 19.2, 7.8Hz, 4H), 2.60 (s, 3H).
79.8%	In tetrahydrofuran at 20℃; Cooling with ice;
55%	In dichloromethane at 20℃; Schlenk technique;
28%	In dichloromethane at 20℃; for 2h;
	With TEA In tetrahydrofuran at 20℃;
	With sodium hydroxide
	With sodium hydroxide at 20℃;
	Alkaline conditions;
	With sodium hydroxide In ethanol at 70 - 80℃; for 0.5h;
	With triethylamine In N,N-dimethyl-formamide at 0℃; Inert atmosphere;	4.2.2 General procedure for the synthesis of 7a-n and 8a-i General procedure: (i) To a solution of aminoacetophenones (5.0 mmol) in anhydrous DMF (10 mL) were added 1.0 equiv of the corresponding acyl chloride (5.0 mmol) and 1.2 equiv of triethylamine (6.0 mmol) at 0 °C in ice-bath under argon atmosphere, and the reaction was allowed to stir until all the starting material had disappeared. Then, the resulting mixture was acidified with 1 M HCl to PH<7 and extracted with ethyl acetate (3 times). The obtained organic phase was washed with 5 % NaHCO3 (2 times) and brine (2 times), dried over Na2SO4 and concentrated in vacuo to give the intermediates 5a-n and 6a-i, which was used directly for the next step.

Reference： [1]El Sayed Aly, Mohamed Ramadan; Abd El Razek Fodah, Hamadah Hamadah; Saleh, Sherif Yousef [European Journal of Medicinal Chemistry, 2014, vol. 76, p. 517 - 530]
[2]Gutti, Gopichand; Kumar, Devendra; Paliwal, Pankaj; Ganeshpurkar, Ankit; Lahre, Khemraj; Kumar, Ashok; Krishnamurthy, Sairam; Singh, Sushil Kumar [Bioorganic Chemistry, 2019, vol. 90]
[3]Ueda, Satoshi; Nagasawa, Hideko [Journal of Organic Chemistry, 2009, vol. 74, # 11, p. 4272 - 4277]
[4]Dou, Xiaodong; Huang, Huixia; Jiang, Lan; Jiao, Ning; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Zhang, Lihe; Zhu, Guiwang [European Journal of Medicinal Chemistry, 2020, vol. 201]
[5]Location in patent: experimental part Li, Hongcai; Wang, Chao; Sanchez, Tino; Tan, Yanmei; Jiang, Chunying; Neamati, Nouri; Zhao, Guisen [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 7, p. 2913 - 2919]
[6]Lee, Sun-Hwa; Nikonov, Georgii I. [Dalton Transactions, 2014, vol. 43, # 23, p. 8888 - 8893]
[7]Hooper, Julian; Watts, Paul [Journal of labelled compounds and radiopharmaceuticals, 2007, vol. 50, # 3, p. 189 - 196]
[8]Summa, Vincenzo; Petrocchi, Alessia; Pace, Paola; Matassa, Victor G.; De Francesco, Raffaele; Altamura, Sergio; Tomei, Licia; Koch, Uwe; Neuner, Philippe [Journal of Medicinal Chemistry, 2004, vol. 47, # 1, p. 14 - 17]
[9]Location in patent: scheme or table Bandgar, Babasaheb P.; Jalde, Shivkumar S.; Korbad, Balaji L.; Patil, Sachin A.; Chavan, Hemant V.; Kinkar, Santosh N.; Adsul, Laxman K.; Shringare, Sadanand N.; Nile, Shivraj H. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, vol. 27, # 2, p. 267 - 274]
[10]Bandgar, Babasaheb P.; Adsul, Laxman K.; Chavan, Hemant V.; Shringare, Sadanand N.; Korbad, Balaji L.; Jalde, Shivkumar S.; Lonikar, Shrikant V.; Nile, Shivraj H.; Shirfule, Amol L. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5649 - 5657]
[11]Bandgar, Babasaheb P.; Hote, Baliram S.; Jalde, Shivkumar S.; Gacche, Rajesh N. [Medicinal Chemistry Research, 2012, vol. 21, # 10, p. 3006 - 3014]
[12]Bandgar, Babasaheb P.; Kinkar, Santosh N.; Chavan, Hemant V.; Jalde, Shivkumar S.; Shaikh, Rafik U.; Gacche, Rajesh N. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 1, p. 7 - 11]
[13]You, Ao; Zhou, Jie; Song, Senchuan; Zhu, Guoxun; Song, Huacan; Yi, Wei [European Journal of Medicinal Chemistry, 2015, vol. 93, p. 255 - 262]

22
[ 54060-30-9 ]
[ 99-03-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With silver hexafluoroantimonate In methanol; lithium hydroxide monohydrate at 120℃; for 24h; Sealed tube;
91%	With C₂₂H₂₀AuN₃O₂P⁽¹⁺⁾*CF₃O₃S^(1-); lithium hydroxide monohydrate; trifluoromethane sulfonic acid silver salt; glacial acetic acid at 100℃; for 10h;
90%	With lithium hydroxide monohydrate at 200℃; for 0.333333h; microwave irradiation;

90%	With 1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidenegold(I) chloride In methanol; lithium hydroxide monohydrate at 110℃; for 6h; Schlenk technique; regioselective reaction;
90%	With 1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidenegold(I) chloride; lithium hydroxide monohydrate In methanol at 110℃; for 6h;	12 Example 12 : 3-aminoacetophenone The catalyst [(IPr) AuCl] (3.1mg, 0.5mol%), 3- amino-phenylacetylene (1mmol), in methanol (1ml) and water (0.5ml) was added successively 25ml reactor.After the reaction mixture was reacted for 6 hours at 110 , cooled to room temperature.Rotary evaporation to remove the solvent, then purified by column chromatography (eluent: petroleum ether / ethyl acetate) to give pure title compound, yield: 90%
85%	With 4-methyl-morpholine; iodine In dimethyl sulfoxide at 120℃; for 16h;	Synthesis of acetophenone derivatives (2a-q) General procedure: A 10 mL reaction flask was charged with terminal alkynes 1a-q (1.0 mmol), I2 (0.3 mmol) and N-methyl morpholine (1.0 mmol) in DMSO (2.0 mL) and then the reaction mixture was heated at 120 °C for 16 h. After completion of the reaction (progress was monitored by TLC; SiO2, hexane/EtOAc = 9:1), the recation mixture was quenched with saturated sodium thiosulphate solution, diluted with water (20 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layer was dried over anhydrous Na2SO4. Solvent was removed under reduced pressure and the remaining residue was purified over silica gel column chromatography using hexane/EtOAc = 4:1 as an eluent to obtain the desired products 2a-q in high yields.
80%	With lithium hydroxide monohydrate In methanol at 150℃; for 14h; Autoclave; Inert atmosphere; Green chemistry;	The general procedure of the reaction General procedure: In a 100 mL capacity of autoclave vessel a 60 mL solution of methanol and water (1:2) was added, further 1 mmol alkynes were added to this solution. The autoclave was three times purged withthe gas and then nally pressurized up to the 11 bar pressure. The reaction mixture was vigorously stirred at 150 °C for continuous 14 h. After the completion of the reaction, the reactor was cooled to room temperature, and then the argon pressure was carefully released to the atmospheric pressure. Methanol from the reaction mixture is removed using rotatory evaporator. After that, the reaction mixture was transferred in a separating funnel, and it wasworked up with ethyl acetate. The organic layer was separatedand dried over Na2SO4. Afterwards, it was filtered and concentrated under reduced pressure. The resulted crude mixture waspuried by silica gel column chromatography using ethyl acetate/n-hexane as eluent, and pure keto product was isolated.
79%	With methanol In lithium hydroxide monohydrate at -5℃; for 0.5h; Irradiation; Green chemistry;	2. Experimental General procedure: To a 100 mL capacity borosilicate immersion well of UV reactor, 80 mL aqueous methanol MeOH:H2O (1:2), alkyne (1 mmol), Rh catalyst (1.5 mol%) was added, and the reaction mixture was cooled to-5 °C. It was irradiated using a Hg vapor UV lamp, 125 W, 289 nm for30 min with continuous stirring. After completion of the reaction, the reaction mixture was left to warm to room temperature and then concentrated in vacuo. The residue was extracted with dichloromethaneand water, the organic phase was collected, dried with anhydrous Na2SO4, concentrated at reduced pressure, and puried by flash columnchromatography using hexane/ethyl acetate as eluent to obtain the corresponding product.The catalyst was synthesized as per the procedure reported in reference 15.
68%	With C₂₀H₁₄AuN₂O₂⁽¹⁺⁾*Cl^(1-); lithium hydroxide monohydrate; trifluoroacetic acid In methanol at 80℃; for 5h; Sealed tube;	2.3 Typical procedure for the hydration of alkynes General procedure: Alkyne (0.5 mmol), catalyst (2.0 mol%), H2O (4.0 equiv., 0.04 mL) and CF3COOH (2.0 mol%) were dissolvedin MeOH (0.4 mL) and the homogeneous solution was stirred in a sealed tube at 80°C for 5 h. After the completion of the reaction, the mixture was cooled to room temperature, and then CH2Cl2 and H2O were added to it. The organic layer was separated and washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified over silica gel by column chromatography (25% EtOAc in hexane).
62%	With 3,4,5-trihydroxybenzoic acid; lithium hydroxide monohydrate at 60℃; for 6h; Sealed tube; Green chemistry;
	With tetrahydrothiophene gold(I) chloride; C₄₂H₃₈O₄P₂S In methanol; lithium hydroxide monohydrate at 120℃; for 3h;

Reference： [1]Wang, Wenlong; Zheng, Anmin; Zhao, Peiqing; Xia, Chungu; Li, Fuwei [ACS Catalysis, 2014, vol. 4, # 1, p. 321 - 327]
[2]Hu, Wenkang; Shan, Liang; Ma, Fudong; Zhang, Yilin; Yang, Yongchun; Wang, Dawei [Inorganic Chemistry Communications, 2019, vol. 109]
[3]Vasudevan, Anil; Verzal, Mary K. [Synlett, 2004, # 4, p. 631 - 634]
[4]Li, Feng; Wang, Nana; Lu, Lei; Zhu, Guangjun [Journal of Organic Chemistry, 2015, vol. 80, # 7, p. 3538 - 3546]
[5]Current Patent Assignee: NANJING UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN106032348, 2016, A Location in patent: Paragraph 0068-0071
[6]Anupam, R. O. Y.; Devi, Elangbam Pinky; Kaldhi, Dhananjaya; Malakar, Chandi C.; Saha, Indranil; Sahoo, Abhishek; Sengupta, Ragini [Asian Journal of Chemistry, 2022, vol. 34, # 6, p. 1592 - 1596]
[7]Ali, Munsaf; Srivastava, Avinash K.; Joshi, Raj K. [Tetrahedron Letters, 2018, vol. 59, # 21, p. 2075 - 2078]
[8]Ali, Munsaf; Srivastava, Avinash K.; Siangwata, Shepherd; Smith, Gregory S.; Joshi, Raj K. [Catalysis Communications, 2018, vol. 115, p. 78 - 81]
[9]Chen, Tingting; Cai, Chun [Catalysis Communications, 2015, vol. 65, p. 102 - 104]
[10]Deng, Tao; Wang, Cheng-Zhang [Catalysis science and technology, 2016, vol. 6, # 19, p. 7029 - 7032]
[11]Chen, Xia; Ye, Xu; Liang, Wen-Yu; Zhou, Qing; Vo-Thanh, Giang; Liu, Ye [Molecular catalysis, 2018, vol. 448, p. 171 - 176]

23
[ 99-03-6 ]
[ 121-33-5 ]
[ 864426-15-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	With barium hydroxide octahydrate In methanol at 27℃;	1 3-Amino-acetophenone (1.0 mmol, 270 mg) was added to a suspension of barium hydroxide octahydrate (1.5 mmol, 945 mg) in methanol (15 raL), and the mixture was stirred for 5 min. Then a solution of vanillin (1 mmol, 304 mg) in methanol (lOmL) was added, and the resulting mixture was stirred for overnight at 27 °C. After completion of the reaction as indicated by TLC, the solvent was removed under vacuum and aqueous layer then extracted with ehtylacetate (3x30 mL). The combined organic phase was dried over Na2S04 and evaporated under vacuum to afford the crude (£)- 1 -(3 -aminophenyl)-3 -(4-hydroxy-3 -methoxyphenyl)-2-propen- 1 -one. The crude product thus obtained was purified by column chromatography using EtoAC-Hexane (30%) as eluent to afford pure compound of 20a (322.8 mg 60%)
60%	Stage #1: 1-(3-aminophenyl)ethanone With barium hydroxide octahydrate In methanol for 0.0833333h; Stage #2: vanillin In methanol at 27℃;	1; 2; 3; 4 Example-1; Example-2; Example-3; Example-4 3-Amino-acetophenone (1.0 mmol, 270 mg) was added to a suspension of barium hydroxide octahydrate (1.5 mmol, 945 mg) in methanol (15 mL), and the mixture was stirred for 5 min. Then a solution of vanillin (1 mmol, 304 mg) in methanol (10 mL) was added, and the resulting mixture was stirred for overnight at 27° C. After completion of the reaction as indicated by TLC, the solvent was removed under vacuum and aqueous layer then extracted with ethylacetate (3×30 mL). The combined organic phase was dried over Na2SO4 and evaporated under vacuum to afford the crude (E)-1-(3-aminophenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-one. The crude product thus obtained was purified by column chromatography using EtoAC-Hexane (30%) as eluent to afford pure compound of 20a (322.8 mg 60%)
49%	With potassium hydroxide In ethanol; water at 20℃; for 10h;

45%	With potassium hydroxide In ethanol at 20℃; for 10h;
45%	With potassium hydroxide In ethanol; water at 5 - 20℃; for 10h;	2.1 4.2.1 1-(3-Amino-phenyl)-3-(4-hydroxy-3-methoxy-phenyl)-propenone (10) A mixture of 4-hydroxy-3-methoxybenzaldehyde (8, 1.5 g, 10.0 mmol) and 3'-aminoacetophenon (9, 1.4 g, 10.0 mmol) is dissolved in 15 mL of ethanol and allowed to stir for several min at 5 °C (ice bath). 10 mL of a 40% KOH solution in water is added dropwise to the flask over several min. The mixture is then allowed to stir at room temperature for approximately 10 h. After the reaction was complete, the reaction mixture was neutralized with a dilute HCl. The solution was extracted with anhydrous ether (3 * 10 mL). The organic layer was concentrated and purified by silica gel column chromatography (CH2Cl2/methanol = 94:6). Yield 45%; mp 154-155 °C; TLC (methylene chloride/methanol = 94:6) Rf = 0.39; 1H NMR (CDCl3): δ 3.82 (2H, s, NH2), 3.97 (3H, s, OCH3), 5.89 (1H, s, OH), 6.88-6.90 (1H, m, NH2C6H4), 6.96 (1H, d, J = 8.21 Hz, CH3OC6H3), 7.13 (1H, d, J = 1.76 Hz, CH3OC6H3), 7.21 (1H, dd, J = 8.21 and 1.80 Hz, CH3OC6H3), 7.28-7.39 (3H, m, NH2C6H4), 7.33 (1H, d, J = 15.63 Hz, CH=CHAr), 7.73 (1H, d, J = 15.63 Hz, CH=CHAr) ppm. 13C NMR (CDCl3): δ 56.0, 110.2, 114.4, 115.1, 118.7, 119.2, 119.9, 123.4, 127.3, 129.4, 139.6, 145.0, 146.9, 147.1, 148.6, 190.9. MS (EI+) (m/z) 269 (M+); Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.72; H, 5.66; N, 5.10.
	With potassium hydroxide In ethanol; water at 0 - 20℃; for 10h;

Reference： [1]Current Patent Assignee: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (IN) - WO2011/86412, 2011, A2 Location in patent: Page/Page column 21
[2]Current Patent Assignee: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (IN) - US2013/66081, 2013, A1 Location in patent: Paragraph 0207; 0211; 0215; 0219
[3]Um, Yumi; Cho, Sungsik; Woo, Ho Bum; Kim, Yong Kee; Kim, Hanna; Ham, Jungyeob; Kim, Su-Nam; Ahn, Chan Mug; Lee, Seokjoon [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 7, p. 3608 - 3615]
[4]Ho, Bum Woo; Shin, Woon-Seob; Lee, Seokjoon; Chan, Mug Ahn [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 16, p. 3782 - 3786]
[5]Park, Chong-Bin; Ahn, Chan Mug; Oh, Sangtae; Kwon, Daeho; Cho, Won-Chul; Shin, Woon-Seob; Cui, Yuan; Um, Ye Sol; Park, Byong-Gon; Lee, Seokjoon [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 20, p. 6673 - 6682]
[6]Location in patent: scheme or table Kamal, Ahmed; Ramakrishna; Raju; Viswanath; Janaki Ramaiah; Balakishan; Pal-Bhadra, Manika [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 16, p. 4865 - 4869]

24
[ 99-03-6 ]
[ 1885-14-9 ]
[ 405905-06-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium carbonate In tetrahydrofuran; water; ethyl acetate at 0 - 20℃;	4.1.6.1. Phenyl-(4-isopropoxyphenyl)carbamate (13a) General procedure: Into a stirringmixture of ethyl acetate (20 mL), tetrahydrofuran (4 mL), water(4 mL), sodium carbonate (0.8 g, 7.9 mmol, 0.6 equiv.), and 4-isopropoxyaniline (2.0 g, 13.2 mmol, 1 equiv.), phenyl chloroformate(2.3 g, 14.5 mmol, 1.1 equiv.) was added dropwise at 0° C.The reaction was stirred at room temperature overnight, then itwas evaporated under reduced pressure and the resultant wasadded into 20 mL water, the precipitate was filtered and washedwith water, then dried under vacuum to afford 3.2 g of 13a as whitesolid; yield: 90%.
	With triethylamine In dichloromethane

Reference： [1]Li, Yingxiu; Ye, Tianyu; Xu, Le; Dong, Yuhong; Luo, Yong; Wang, Chu; Han, Yufei; Chen, Ke; Qin, Mingze; Liu, Yajing; Zhao, Yanfang [European Journal of Medicinal Chemistry, 2019, vol. 181]
[2]De Lucca, George V.; Ui, Tae Kim; Vargo, Brian J.; Duncia, John V.; Santella III, Joseph B.; Gardner, Daniel S.; Zheng, Changsheng; Liauw, Ann; Wang, Zhang; Emmett, George; Wacker, Dean A.; Welch, Patricia K.; Covington, Maryanne; Stowell, Nicole C.; Wadman, Eric A.; Das, Anuk M.; Davies, Paul; Yeleswaram, Swamy; Graden, Danielle M.; Solomon, Kimberly A.; Newton, Robert C.; Trainor, George L.; Decicco, Carl P.; Ko, Soo S. [Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 2194 - 2211]

25
[ 527-69-5 ]
[ 99-03-6 ]
[ 60943-81-9 ]

Yield	Reaction Conditions	Operation in experiment
61%	With pyridine In chloroform at 20℃;	3.2.2. general Procedure for the Preparation of 8-15 General procedure: A solution of the substituted aniline (18 mmol) in 30 mLof dry CHCl3 was added dropwise to a solution of 1 or 2 (9mmol) in 20 mL dry of CHCl3 and 3 mL of dry pyridine at -2°C. The resulting solution was stirred overnight. After completion of the reaction, 30 mL of 0.1 M NaHCO3 solution was added onto the solution with stirring, then the organic layer was separated and dried over Na2SO4, and the solvent was evaporated under reduced pressure. The product was washed with concentrated HCl (30 mL). Using the general procedure, the following compounds were synthesized
41.1%	In tetrahydrofuran at 20℃; Cooling with ice;
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; for 8h;	1 Example 1; FURAN-2-CARBOXYLIC acid (3-acetyl-phenyl) -amide. To a solution of 1 g of 3- aminoacetophenone in 20 ML of CH2C12 was added 5 mL of ethyl-di-iso-propylamine. To the stirred reaction mixture was then added 1 mL of 2-furoyl chloride which was allowed to stir at 25 °C for 8 h. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (CH2C12) to yield 900 mg of furan-2-carboxylic acid (3-acetyl-phenyl) -amide as a white SOLID. 1H NMR (CDC13, 500 MHz) 8 8.11 (1 H, br s), 8.09 (1H, t, J = 2 HZ), 7.93 (1 H, m), 7.66 (1H, m), 7.47 (1 H, m), 7.20 (1 H, m), 6.52 (1 H, m), 2.56 (3H, s) ppm.

	With sodium hydroxide
	With sodium hydroxide at 20℃;

Reference： [1]Abu-Qatouseh, Luay; Idrees, Gada; Joshi, Rajendra; Khanfar, Monther; Mallah, Eyad; Mubarak, Mohammsad S.; Sweidan, Kamal; Tahir, Muhammad Nawaz [Letters in Organic Chemistry, 2022, vol. 19, # 4, p. 314 - 325]
[2]Location in patent: experimental part Li, Hongcai; Wang, Chao; Sanchez, Tino; Tan, Yanmei; Jiang, Chunying; Neamati, Nouri; Zhao, Guisen [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 7, p. 2913 - 2919]
[3]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - WO2004/41789, 2004, A1 Location in patent: Page 70
[4]Location in patent: scheme or table Bandgar, Babasaheb P.; Jalde, Shivkumar S.; Korbad, Balaji L.; Patil, Sachin A.; Chavan, Hemant V.; Kinkar, Santosh N.; Adsul, Laxman K.; Shringare, Sadanand N.; Nile, Shivraj H. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, vol. 27, # 2, p. 267 - 274]
[5]Bandgar, Babasaheb P.; Adsul, Laxman K.; Chavan, Hemant V.; Shringare, Sadanand N.; Korbad, Balaji L.; Jalde, Shivkumar S.; Lonikar, Shrikant V.; Nile, Shivraj H.; Shirfule, Amol L. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5649 - 5657]

26
[ 99-03-6 ]
[ 230955-75-6 ]
acetic acid 4-(3-acetylphenylamino)-7-methoxy-6-quinazolinyl ester hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In isopropyl alcohol; for 5h;Heating / reflux;	1) A solution (200 ML) of acetic acid 4-chloro-7-methoxy-6-quinazolinyl ester [described in U.S. Pat. Nos. 5,770,599 and 5,770,603] (3.74 g, 14.8 mmol) and 3-aminoacetophenone (2.0 g, 14.8 mmol) in isopropanol was heated under reflux for 5 hrs.After allowing to stand to cool, the precipitate was collected by filtration to give acetic acid 4-(3-acetylphenylamino)-7-methoxy-6-quinazolinyl ester hydrochloride (4.78 g, yield as monohydrochloride 83%).To a solution (100 ML) of this compound (3.0 g, 7.74 mmol) in methanol was added 28% aqueous ammonia (2 ML), and the mixture was stirred at room temperature for 4 hrs and then refluxed.The produced precipitate was collected by filtration and dried under reduced pressure to give 1-[3-(6-hydroxy-7-methoxy-4-quinazolinylamino)phenyl]ethanone (2.07 g, 87%).

Reference： [1]Patent: US2004/116422,2004,A1 .Location in patent: Page/Page column 48

27
[ 10147-36-1 ]
[ 99-03-6 ]
[ 844679-65-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine In dichloromethane at 20℃; for 20h;	14 Example 14: General procedure for the preparation of N- methyl-enamine-sulfonamides of general formula (VII) following Scheme 3 N- (3-ACETYLPHENYL)-L-PROPANE-SULFONAMIDE 1 g (7.4 mmol) of 3-aminoacetophenone were dissolved in 35 ml of dry dichloromethane. To the resultant solution cooled at 0°C 0. 89 ml (11.09 mmol) of anhydrous pyridine and 1.26 g (8.87 mmol) of 1-PROPANESULFONIC acid chloride were added. After stirring the reaction mixture for 20 h at room temperature and under inert atmosphere, 15 ml of water were added. The two layers were separated, and the aqueous layer was washed with 2X15 ml of dichloromethane. The organic layers were washed with 30 ml of water and dried over anhydrous sodium sulfate. The dichloromethane layer was evaporated to dryness to yield a yellow solid, 1. 8 g (yield= 100%) of N- (3-ACETYLPHENYL)-1-PROPANE-SULFONAMIDE which was directly used for the following reaction. N- [3- [3- (dimethylamino)-l-oxo-2-propenyl] phenyl]-N-methyl- 1-propanesulfonamide 1 g (4.14 mmol) of N- (3-ACETYLPHENYL)-L-PROPANE-SULFONAMIDE were dissolved in 10 ml of N, N-dimetylformamide. To the resultant solution 2.77 ml (20.74 mmol) of N, N- dimethylformamide dimethyl acetal were added and heated at 150°C for 2 h. The solvent was removed by reduced pressure distillation to yield an oil, which was treated with a mixture of ethyl acetate-ethyl ether. A small quantity of a solid precipitated which was discarded The filtrate was evaporated to dryness, dissolved in dichloromethane, and the organic layer was washed with 4X50 ml of water and evaporated to dryness. 1.23 g (YIELD = 96%) of N- [3- [3- (DIMETHYLAMINO)-1-OXO-2-PROPENYL] PHENYL]-N-METHYL-1- propane-sulfonamide were obtained.

Reference： [1]Current Patent Assignee: FERRER INTERNACIONAL SA - WO2005/14597, 2005, A1 Location in patent: Page/Page column 46; 47

28
sodium thiomethoxide [ No CAS ]
[ 99-03-6 ]
3'-thiomethylacetophenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium nitrite In hydrogenchloride; water	44 N-(3-Phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride N-(3-Phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride 3'-Aminoacetophenone (2.7 g, 20 mmol) was dissolved in 4 mL of concentrated HCl, 4 g of ice and 8 mL of water. The solution was cooled to 0C, and sodium nitrite (1.45 g, 21 mmol) dissolved in 3-5 mL of water was added over 5 minutes while maintaining the temperature below 6° C. Sodium thiomethoxide (1.75 g, 25 mmol) was dissolved in 5 mL of water and cooled to 0° C. To this solution was added the diazonium salt over 10 minutes while maintaining the temperature below 10° C. The reaction was stirred for an additional hour while allowing the temperature to rise to ambient. The reaction mixture was partitioned between ether and water. The ether layer was separated and washed with sodium bicarbonate and sodium chloride, and dried over sodium sulfate. The ether was evaporated to give a 74% yield of 3'-thiomethylacetophenone.
74%	With sodium nitrite In hydrogenchloride; water	2 N-(3-phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride N-(3-phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride 3'-Aminoacetophenone (2.7 g, 20 mmol) was dissolved in 4 mL of concentrated HCl, 4 g of ice and 8 mL of water. The solution was cooled to 0° C., and sodium nitrite (1.45 g, 21 mmol) dissolved in 3-5 mL of water was added over 5 minutes while maintaining the temperature below 6° C. Sodium thiomethoxide (1.75 g, 25 mmol) was dissolved in 5 mL of water and cooled to 0° C. To this solution was added the diazonium salt over 10 minutes while maintaining the temperature below 10° C. The reaction was stirred for an additional hour while allowing the temperature to rise to ambient. The reaction mixture was partitioned between ether and water. The ether layer was separated and washed with sodium bicarbonate and sodium chloride, and dried over sodium sulfate. The ether was evaporated to give a 74% yield of 3'-thiomethylacetophenone.
74%	With sodium nitrite In hydrogenchloride; water	44 N-(3-Phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride N-(3-Phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride 3'-Aminoacetophenone (2.7 g, 20 mmol) was dissolved in 4 mL of concentrated HCl, 4 g of ice and 8 mL of water. The solution was cooled to 0° C., and sodium nitrite (1.45 g, 21 mmol) dissolved in 3-5 mL of water was added over 5 minutes while maintaining the temperature below 6° C. Sodium thiomethoxide (1.75 g, 25 mmol) was dissolved in 5 mL of water and cooled to 0° C. To this solution was added the diazonium salt over 10 minutes while maintaining the temperature below 10° C. The reaction was stirred for an additional hour while allowing the temperature to rise to ambient. The reaction mixture was partitioned between ether and water. The ether layer was separated and washed with sodium bicarbonate and sodium chloride, and dried over sodium sulfate. The ether was evaporated to give a 74% yield of 3'-thiomethylacetophenone.

74%	With sodium nitrite In hydrogenchloride; water	7 N-(3-phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride N-(3-phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride 3'-Aminoacetophenone (2.7 g, 20 mmol) was dissolved in 4 mL of concentrated HCl, 4 g of ice and 8 mL of water. The solution was cooled to 0° C., and sodium nitrite (1.45 g, 21 mmol) dissolved in 3-5 mL of water was added over 5 minutes while maintaining the temperature below 6° C. Sodium thiomethoxide (1.75 g, 25 mmol) was dissolved in 5 mL of water and cooled to 0° C. To this solution was added the diazonium salt over 10 minutes while maintaining the temperature below 10° C. The reaction was stirred for an additional hour while allowing the temperature to rise to ambient. The reaction mixture was partitioned between ether and water. The ether layer was separated and washed with sodium bicarbonate and sodium chloride, and dried over sodium sulfate. The ether was evaporated to give a 74% yield of 3'-thiomethylacetophenone.
74%	With sodium nitrite In hydrogenchloride; water	44 N-(3-Phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride N-(3-Phenylpropyl)-1-(3-thiomethylphenyl)ethylamine hydrochloride 3'-Aminoacetophenone (2.7 g, 20 mmol) was dissolved in 4 mL of concentrated HCl, 4 g of ice and 8 mL of water. The solution was cooled to 0° C., and sodium nitrite (1.45 g, 21 mmol) dissolved in 3-5 mL of water was added over 5 minutes while maintaining the temperature below 6° C. Sodium thiomethoxide (1.75 g, 25 mmol) was dissolved in 5 mL of water and cooled to 0° C. To this solution was added the diazonium salt over 10 minutes while maintaining the temperature below 10° C. The reaction was stirred for an additional hour while allowing the temperature to rise to ambient. The reaction mixture was partitioned between ether and water. The ether layer was separated and washed with sodium bicarbonate and sodium chloride, and dried over sodium sulfate. The ether was evaporated to give a 74% yield of 3'-thiomethylacetophenone.

Reference： [1]Current Patent Assignee: MASS GENERAL BRIGHAM INC - US6313146, 2001, B1
[2]Current Patent Assignee: MASS GENERAL BRIGHAM INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED - US6001884, 1999, A
[3]Current Patent Assignee: SUSAN BROWN - US5763569, 1998, A Current Patent Assignee: MASS GENERAL BRIGHAM INC - US6031003, 2000, A Current Patent Assignee: SUSAN BROWN - US5688938, 1997, A
[4]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US6211244, 2001, B1
[5]Current Patent Assignee: MASS GENERAL BRIGHAM INC - US6011068, 2000, A

29
[ 99-03-6 ]
[ 15411-43-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium borohydrid; In isopropyl alcohol;	Procedure: 3-Aminostyrene 135 g (1 mol) of 3-aminoacetophenone are suspended in 1,000 ml of isopropanol, and 19 g (0.5 mol) of sodium borohydride are slowly added. The reaction mixture is stirred at room temperature for 48 hours and then brought to a pH of 5 with concentrated hydrochloric acid, while cooling with ice. The salt which is precipitated is filtered off with suction, and the slightly reddish solution is concentrated on a rotary evaporator under a water pump vacuum. The desired 1-(3-aminophenyl)ethanol crystallizes overnight in the cold, is filtered off with suction and dried. The alcohol is subsequently dehydrated at 300 C. by means of an aluminium oxide catalyst in a heated tube. The product is taken up in water and extracted from the aqueous phase by shaking with ether, the organic phase is dried over sodium sulphate and the solvent is evaporated. Yield: 77.3 g.

Reference： [1]Patent: US5037961,1991,A

30
[ 99-03-6 ]
[ 592-34-7 ]
[ 72531-03-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With pyridine In acetone for 3h; Reflux;	4.2.2.1. General procedure for the preparation of alkyl (3-/4-acetylphenyl)carbamates (3a-6a). General procedure: A solution of an appropriatealkyl chloroformiate (37 mmol) in acetone (5 mL) was addeddropwise to a stirred solution of 3-aminoacetophenone (5.00 g;37 mmol) or 4-aminoacetophenone (5.00 g; 37 mmol) and pyridine(3.0 mL; 37 mmol) in acetone (20 mL), and then the mixture washeated to reflux for 3 h. The solvent was removed at reducedpressure, and the resulting solid was washed with water, andrecrystallized from EtOH.4.2.2.1.1. Butyl (3-acetylphenyl)carbamate (3a). White solid,Yield 91%, m.p. 58-59 °C [53-55 °C [74]. 1H NMR (DMSO-d6) δ 0.92(t, 3H, -CH3, J 6.2 Hz), 1.33e1.46 (m, 2H, -CH2-), 1.54e1.64 (m, 2H,-CH2-), 2.54 (s, 3H, -CH3), 4.09 (t, 2H, -CH2-, J 6.6 Hz), 7.42 (t, 1H,ArH, J 7.9 Hz), 7.60 (d, 1H, ArH, J 7.7 Hz), 7.68 (d, 1H, ArH,J 7.7 Hz), 8.07 (s, 1H, ArH), 9.83 (s, 1H, NH). 13C NMR (DMSO-d6)δ 197.5, 153.6, 139.6, 137.4, 129.0, 122.6, 122.3, 117.3, 63.9, 30.5, 26.6,18.5, 13.5.
91%	With pyridine In acetone for 3h; Reflux;	3.2.1. General Procedure For the Preparation of Alkyl (3-/4-Acetylphenyl)carbamates (3a-h) General procedure: Into a stirred solution of 3-aminoacetophenone 1a (CAS Registry Number 99-03-6; 5.00 g, 37 mmol)or 4-aminoacetophenone 1b (CAS Registry Number 99-92-3; 5.00 g, 37 mmol) and pyridine (3.0 mL,37 mmol) in 20 mL of acetone, a solution of methyl chloroformate 2a (CAS Registry Number 79-22-1;3.5 mL, 37 mmol), ethyl chloroformate 2b (CAS Registry Number 541-41-3; 4.0 mL, 37 mmol), propylchloroformate 2c (CAS Registry Number 109-61-5; 4.5 mL, 37 mmol) or butyl chloroformate 2d (CASRegistry Number 592-34-7; 5.0 mL, 37 mmol) in 5 mL of acetone, was added dropwise. The particularmixture was heated to reflux for 3 h [28]. When the reaction was completed (TLC control), the solventswere removed in vacuo, crude solid products 3a-h were washed with distilled water and recrystallizedfrom absolute ethanol. Full characterization data for the compounds 3a-h (Scheme 1), isolated ascolourless solids, are given below.
	With N-ethyl-N,N-diisopropylamine In dichloromethane	9 [3-[3-(Dimethylamino)-1-oxo-2-propenyl]phenyl]carbamic acid, butyl ester EXAMPLE 9 [3-[3-(Dimethylamino)-1-oxo-2-propenyl]phenyl]carbamic acid, butyl ester A mixture of 27.03 g of m-aminoacetophenone, 25.85 g of diisopropylethylamine, 27.32 g of n-butyl chloroformate and 300 ml of dichloromethane was reacted as described in Example 1, giving 42.10 g of (3-acetylphenyl)carbamic acid, butyl ester, mp 59°-60° C.

With pyridine In acetone for 3h; Reflux;

4.3.1. General procedure for the preparation of alkyl (2-/3-acetylphenyl)carbamates (14a-21a) General procedure: A solution of an appropriate alkyl chloroformiate (37 mmol) inacetone (5 mL) was added dropwise to a stirred solution of 2-aminoacetophenone(5.00 g; 37 mmol) or 3-aminoacetophenone (5.00 g;37 mmol) and pyridine (3.0 mL; 37 mmol) in acetone (20 mL), and thenthe mixture was heated to reflux for 3 h. The solvent was removed atreduced pressure, and the resulting solid was washed with water, andrecrystallized from EtOH.

Reference： [1]Vettorazzi, Marcela; Angelina, Emilio; Lima, Santiago; Gonec, Tomas; Otevrel, Jan; Marvanova, Pavlina; Padrtova, Tereza; Mokry, Petr; Bobal, Pavel; Acosta, Lina M.; Palma, Alirio; Cobo, Justo; Bobalova, Janette; Csollei, Jozef; Malik, Ivan; Alvarez, Sergio; Spiegel, Sarah; Jampilek, Josef; Enriz, Ricardo D. [European Journal of Medicinal Chemistry, 2017, vol. 139, p. 461 - 481]
[2]Gonec, Tomás; Malík, Ivan; Csöllei, Jozef; Jampílek, Josef; Stolaríková, Jirina; Solovic, Ivan; Miku, Peter; Keltoová, Stanislava; Kollár, Peter; O'Mahony, Jim; Coffey, Aidan [Molecules, 2017, vol. 22, # 12]
[3]Current Patent Assignee: PFIZER INC - US4654347, 1987, A
[4]Campos, Ludmila E.; Garibotto, Francisco M.; Angelina, Emilio; Kos, Jiri; Tomašič, Tihomir; Zidar, Nace; Kikelj, Danijel; Gonec; Marvanova, Pavlina; Mokry, Petr; Jampilek; Alvarez, Sergio E.; Enriz, Ricardo D. [Bioorganic Chemistry, 2019, vol. 91]

31
[ 39499-34-8 ]
[ 99-03-6 ]
3'-acetyl-5-methyl-3-isoxazolecarboxanilide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In potassium carbonate; acetone;	Part A Preparation of 3'-acetyl-5-methyl-3-isoxazolecarboxanilide. 1/4 hydrate STR8 A solution of 5-methyl-3-isoxazolecarbonyl chloride (14.5 g) in acetone (30 ml) was added to a solution of m-aminoacetophenone (13.8 g) in acetone (280 ml) in the presence of anhydrous potassium carbonate (21.0 g). The mixture was stirred for 1/2hour, and then diluted with water. The precipitated product was filtered, washed with water and dried. Yield = 20.5 g (83%), m.p. 188-190. Analysis %: Found: C, 62.77; H, 5.00; N, 10.89. Calculated for C13 H12 N2 O3.1/4H2 O: C, 62.77; H, 5.03; N, 11.26.

Reference： [1]Patent: US4137321,1979,A

32
[ 431-47-0 ]
[ 99-03-6 ]
[ 56915-87-8 ]

Yield	Reaction Conditions	Operation in experiment
~ 85%	In methanol; at 20℃; for 2.5h;	In the 100 mL rounded bottom flask, the starting material, about 10 mmol of 3'-aminoacetophenone was dissolved in methanol solvent. Then methyl trifluoroacetate, about 1.2 eq was added for about 30 minutes at room temperature, and stirred for about 2 hours. After confirming reaction completion using Thin Layer Chromatography (TLC), the reaction was completed by using a small amount of water. Then, the solvent was removed under reduced pressure. The residue was dissolved in about 50 mL of ethyl acetoacetate, washed twice with about 30 ml of water, dried with sodium sulfate anhydride, and distilled under reduced pressure. 3-Acetyl-trifluoroacetylamonobenzene was obtained in a form of about 85% brown oil. Rf = 0.39 (Hexane/EtOAc = 1/1), 1 H NMR (300 MHz, CDCl3) delta 7.70 (s, 1 H, NH), 7.33-7.14 (m, 4 H, aromatic), 2.13 (s, 3H)
85%	In methanol; at 20℃; for 2.5h;	Experimental Example 1; Synthesis of Halonitrophenyl Compound; (a) Synthesis of 3-acetyl-trifluoroacetylaminobenzene; 10 mmol of 3'-aminoacetophenone as a starting material was dissolved in a methanol solvent in a 100 mL round-bottomed flask and 1.2 equivalents (eq) of methyl trifluoroacetate was added dropwise thereto over 30 minutes at room temperature, and subsequently the reaction mixture was stirred for 2 hours. After the completion of the reaction was confirmed by TLC, a small amount of water was added to terminate the reaction. Then, the solvent was removed under reduced pressure. The residue was dissolved in 50 mL of ethyl acetate and washed twice with 30 mL of water, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain the desired 3-acetyl-trifluoroacetylaminobenzene (85%) as a brown oil.Rf=0.39 (Hexane/EtOAc=1/1), 1H NMR (300 MHz, CDCl3) delta 7.70 (s, 1H, NH), 7.33-7.14 (m, 4H, aromatic), 2.13 (s, 3H)

Reference： [1]Doklady Chemistry,2011,vol. 439,p. 209 - 212
[2]Russian Journal of General Chemistry,2012,vol. 82,p. 874 - 879
[3]Patent: EP1956028,2008,A2 .Location in patent: Page/Page column 29
[4]Patent: US7566773,2009,B2 .Location in patent: Page/Page column 12

33
[ 99-03-6 ]
[ 1166988-10-8 ]
[ 149914-98-7 ]

Yield	Reaction Conditions	Operation in experiment
1: 42% 2: 50%	With N-Bromosuccinimide In 1,4-dioxane at 20℃; for 1h;
1: 7 %Chromat. 2: 90 %Chromat.	With N-Bromosuccinimide In dimethyl sulfoxide at 20℃;

Reference： [1]Wang, Long; Priebbenow, Daniel L.; Chen, Xiao Yun; Pan, Fang-Fang; Bolm, Carsten [European Journal of Organic Chemistry, 2015, vol. 2015, # 15, p. 3338 - 3343]
[2]Location in patent: experimental part Bartoli, Sandra; Cipollone, Amalia; Squarcia, Antonella; Madami, Andrea; Fattori, Daniela [Synthesis, 2009, # 8, p. 1305 - 1308]

34
[ 99-03-6 ]
[ 1166988-10-8 ]
[ 149914-98-7 ]
[ 37148-51-9 ]

Yield	Reaction Conditions	Operation in experiment
1: 28 %Chromat. 2: 66 %Chromat. 3: 6 %Chromat.	With N-Bromosuccinimide In DCE at 20℃;

Reference： [1]Location in patent: experimental part Bartoli, Sandra; Cipollone, Amalia; Squarcia, Antonella; Madami, Andrea; Fattori, Daniela [Synthesis, 2009, # 8, p. 1305 - 1308]

35
[ 99-03-6 ]
[ 98-59-9 ]
[ 1198088-94-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine In dichloromethane for 2h;	30.a Example 30. 3-(2-Guanidinothiazol-4-yl)phenyl 4-^-butylbenzenesulfonate (17g). (a) 3-Acetylphenyl 4-^-butylbenzenesulfonate (15g).; 4-t-Butyl-benzenesulfonyl chloride (I g, 4.29 mmol) was added to a solution of 3- aminoacetophenone (585 mg, 4.29 mmol), triethylamine (1 mL) and N,N-dimethyl-4- aminopyridine (10 mg, cat.) in dichloromethane. The reaction was allowed to stir for 2h and was then quenched with water and washed with IM HCl. The organic layer was then dried over magnesium sulfate, filtered and evaporated under reduced pressure to yield 1.37 g (96%) of a white solid. IH-NMR (CDCl3) δ 7.84 (d, IH, J=7.7Hz), 7.75 (d, 2H, J=8.4Hz), 7.54 (d, 2H, J=8.4Hz), 7.44 (s, IH), 7.41 (d, IH, J=7.9Hz), 7.26 (s, IH), 2.49 (s, 2H), 1.34 (s, 9H). 13CNMR (DMSO): δ 196.300, 158.650, 149.707, 138.496, 131.941, 129.914, 128.351, 127.116, 126.757, 126.235, 122.187, 35.351, 30.944, 26.539.

Reference： [1]Current Patent Assignee: GEORGETOWN UNIVERSITY - WO2009/146013, 2009, A1 Location in patent: Page/Page column 80

36
[ 13472-00-9 ]
[ 67-43-6 ]
[ 99-03-6 ]
[ 254759-79-0 ]
[ 254759-80-3 ]

Yield	Reaction Conditions	Operation in experiment
		To solution of DTPA (143 mg, 0.4 mmol) in 10 mL dry DMSO and 2 mL dry triethylamine was added a solution of 3-aminoacetophenone (3AAP, 54 mg, 0.4 mmol) in 5 mL DMSO. The mixture was stirred at room temperature for 0.5 h and then treated with a solution of 4-aminophenethylamine (4APEA, 53 mg, 0.4 mmol) in 5 mL DMSO. The mixture was allowed to stir at room temperature for an additional 3 h and then evaporated dryness. The oily residue was chromatographed on reversed-phase C18 hplc (using a step gradient of 0 to 60% acetonitrile in 0.1% TFA buffer) to give, after lyophilization, 1 as a cream colored solid and 5 as a pale yellow solid. Compound 1 was obtained in 59 mg yield. 1H-NMR (CD3OD): d 2.60 (3H, s), 3.1-3.5 (10H, m), 3.6 (2H, s), 3.65 (2H, s), 3.71 (2H, s), 4.42 (2H, s), 7.42 (1H, dd), 7.75 (1H, dd), 7.83; (1H, dd), 8.31 (1H, d); MS: m/z 511 (M-H), Compound 5 was obtained in 16 mg, yield. 1H-NMR (CD3OD): d 2.62 (3H, s), 2.73 (2H, t), 3.21 (2H, t), 3.3-3.55 (12H, m), 3.65 (2H, s), 3.74 (2H, s), 4.35 (2H, s), 7.13 (4H, s), 7.41 (1H, dd), 7.75 (1H, dd), 7.83 (1H, dd), 8.32 (1H,d); MS: m/z 682 (M+3NH4), 683 (MH+3NH4)

Reference： [1]Patent: US6740756,2004,B1 .Location in patent: Page column 11

37
[ 99-03-6 ]
[ 100-52-7 ]
(E)-1-(3-aminophenyl)-3-phenylprop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium hydroxide In ethanol at 20℃;
53.4%	With sodium hydroxide In 1,4-dioxane; methanol at 20℃;	3.3.1. Method I (Compounds 1-6, 10-18) General procedure: In a round bottomed flask 0.24 g (6.00 mmol) of sodium hydroxide was dissolved in 10 mLmethanol and 10 mL dioxane. After that, an appropriate aminoacetophenone (3.67 mmol) and thecorresponding benzaldehyde (3.67 mmol) were added. Reactions were performed in room temperatureon a magnetic stirrer until complete conversion of the substrates. After that, the reaction mixtureswere poured into ice water. Precipitated crystals were collected and purified by liquid columnchromatography on silica gel using mixtures of hexane-acetone, hexane-ethyl acetate or hexane-ethylacetate-methylene chloride as eluents. Compounds 4 and 6 were synthesized at 2.5 times smaller scale.
33%	With potassium hydroxide In water at 20℃;	General procedure for synthesis of 4a-4e General procedure: To a solution of substituted acetophenone (10 mmol) in rectified spirit (30 mL), benzaldehyde (1.01 mL, 10 mmol) was added followed by an aqueous solution of 10 % KOH (10 mL). The mixture was stirred and kept overnight at room temperature. The contents of the reaction mixture were poured into crushed ice and acidified with dil. HCl (0.1-0.2 N). The precipitated chalcone derivative was filtered off and recrystallised from rectified spirit. Column chromatography (10-20 % EtOAc/cyclohexane) was performed whenever recrystallisation failed to sufficiently purify the target compound.

	With sodium hydroxide In methanol at 20℃;
	With sodium hydroxide In ethanol; water at 0 - 20℃; for 2h;
	With sodium hydroxide In ethanol at 20℃;	General procedure: Compounds were prepared using 5.0 mmol of aminoacetophenonesand benzaldehydes on the ethanolic solution of sodium hydroxide (1.0mol L-1). Mixtures were stirred at room temperature and monitored byTLC, using hexanes/ethyl acetate as the mobile phase. Crude productswere filtered and purified by chromatography on a silica gel columnusing hexanes and ethyl acetate. All compounds were identified using 1Hand 13C NMR spectral data obtained from a Bruker Avance III spectrometer(14.0 T), using DMSO-d6 as solvent.

Reference： [1]Trein, Márcia Rodrigues; Rodrigues e Oliveira, Lígia; Rigo, Graziela Vargas; Garcia, Mayara Aparecida Rocha; Petro-Silveira, Brenda; da Silva Trentin, Danielle; Macedo, Alexandre José; Regasini, Luis Octávio; Tasca, Tiana [Parasitology Research, 2019, vol. 118, # 2, p. 607 - 615]
[2]Kozłowska, Joanna; Potaniec, Bartłomiej; Baczyńska, Dagmara; Zarowska, Barbara; Anioł, Mirosław [Molecules, 2019, vol. 24, # 22]
[3]Iqbal, Hiba; Prabhakar, Visakh; Sangith, Atul; Chandrika, Baby; Balasubramanian, Ranganathan [Medicinal Chemistry Research, 2014, vol. 23, # 10, p. 4383 - 4394]
[4]Location in patent: scheme or table Tomar; Bhattacharjee; Kamaluddin; Rajakumar; Srivastava, Kumkum; Puri [European Journal of Medicinal Chemistry, 2010, vol. 45, # 2, p. 745 - 751]
[5]Prasanna, Ramanathan; Guha, Somraj; Sekar, Govindasamy [Organic Letters, 2019, vol. 21, # 8, p. 2650 - 2653]
[6]Santos, Mariana Bastos dos; Carvalho Marques, Beatriz; Miranda Ayusso, Gabriela; Rocha Garcia, Mayara Aparecida; Chiquetto Paracatu, Luana; Pauli, Ivani; Silva Bolzani, Vanderlan; Defini Andricopulo, Adriano; Farias Ximenes, Valdecir; Zeraik, Maria Luiza; Regasini, Luis Octavio [Bioorganic Chemistry, 2021, vol. 110]

38
[ 99-03-6 ]
[ 73183-34-3 ]
[ 214360-49-3 ]

Yield	Reaction Conditions	Operation in experiment
65%	With tert.-butylnitrite; dibenzoyl peroxide In acetonitrile at 20℃; for 2h;
65%	With tert-butyl nitrite; benzoyl peroxide In acetonitrile MeCN, CH3C(O)C6H4NH2 (1 mmol) and tBuONO (1.5 mmol) added to B2pin2 (1 mmol) and benzoyl peroxide (0.02 mmol), mixt. stirred at room temp. for 2h; soln. concd. (under reduced pressure), residue chromd.;
61%	Stage #1: 1-(3-aminophenyl)ethanone With tetrafluoroboric acid; sodium nitrite In water at 0℃; for 1.08333h; Stage #2: bis(pinacol)diborane With triphenylphosphine In acetonitrile at 20℃; for 24h; Inert atmosphere; Schlenk technique;	Typical procedure for the borylation of arenediazonium salts The arylamine (10 mmol) was dissolved in a mixture of 5 mL of distilled water and 3:4 mL of 50% tetrafluoroboric acid. After cooling the reaction mixture to 0 °C in an ice bath, sodium nitrite (0:69 g in 2 mL of distilled water ) was added dropwise within 5 min. The resulting mixture was stirred for 1 h, and the precipitate was collected by filtration and redissolved in the minimum amount of acetone. Diethyl ether was added until precipitation of the arenediazonium tetrafluoroborate, which was filtered, washed several times with diethylether, and dried under vacuum. An arenediazonium salt (1:5 mmol), bis(pinacolato)diborane(1 mmol) and PPh3 (2:0 eq.) were weighed in a 25 LSchlenk round bottom flask under nitrogen atmosphere. Then 3 mL of acetonitrile was added by syringe. The resulting solution was stirred at room temperature. The reaction progress was monitored by GC-MS. After the completion of the reaction,the solution was filtered though a short column of silica gel and the column washed with ethyl acetate. The filtrate was concentrated under reduced pressure to leave a crude product, which was purified by flash column chromatography on silica gel to afford the final products.

Reference： [1]Mo, Fanyang; Jiang, Yubo; Qiu, Di; Zhang, Yan; Wang, Jianbo [Angewandte Chemie - International Edition, 2010, vol. 49, # 10, p. 1846 - 1849]
[2]Mo, Fanyang; Jiang, Yubo; Qiu, Di; Zhang, Yan; Wang, Jianbo [Angewandte Chemie - International Edition, 2010, vol. 49, # 10, p. 1846 - 1849]
[3]Chen, Shuangshuang; Pan, Zhangjin; Wang, Yan [Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2014, vol. 69, # 9-10, p. 982 - 986]

39
[ 99-03-6 ]
[ 100-52-7 ]
[ 108714-19-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With ethanol; sodium hydroxide at 20℃; for 3h;
55%	With sodium hydroxide In ethanol at 20℃;	Synthesis General procedure: Reagents and solvents were purchased from Merck. Series of 17 chalcones was synthesized by Claisen-Schmidt aldol condensation, according to protocol reported by Santos and coauthors with minor modifications [15]. Reactions were carried out at room temperature using 5.0mmol of respective benzaldehyde derivatives and 5.0mmol of respective aminoacetophenones, which were dissolved in ethanol (50mL). Sodium hydroxide in ethanol (1mol L-1) was added as catalyst solution. Reagents conversion was monitored by thin layer chromatography. Crude products were poured onto ice from distilled and deionized water and filtered. All compounds were purified over silica gel chromatography column eluted with mixtures of hexane and ethyl acetate. Melting point of chalcones was measured on open capillaries on Melt Temperature apparatus MS Tecnopon PFM-II. UV-Vis spectra and chromatograms were obtained in High Performance Liquid Chromatography with Diode Array Detector (HPLC-DAD) Agilent Technologies 1220 Infinity equipment, photodiode array system (Agilent Technologies Model 1260 Infinity) and Agilent Zorbax Eclipse Plus C-18 column (250mm×4.6mm, 5µL) using methanol:water (3:1) as mobile phase (1.0mL/min). NMR spectra were obtained in two spectrometers: Bruker Avance III (600MHz) and Bruker Avance III (400MHz), using deuterated dimethyl sulfoxide (DMSO- d6) as internal reference. Low mass spectrometry by electrospray ionization spectra were performed on Bruker Amazon ESI-IT.
	With sodium hydroxide In methanol

Alkaline conditions;

Reference： [1]Location in patent: experimental part Karaman, Isa; Gezegen, Hayreddin; Guerdere, M. Burcu; Dingil, Alparslan; Ceylan, Mustafa [Chemistry and biodiversity, 2010, vol. 7, # 2, p. 400 - 408]
[2]Garcia, Mayara A.R.; Theodoro, Reinaldo S.; Sardi, Janaina C.O.; Santos, Mariana B.; Ayusso, Gabriela M.; Pavan, Fernando R.; Costa, Alan R.; Santa Cruz, Lucas M.; Rosalen, Pedro L.; Regasini, Luis O. [Bioorganic Chemistry, 2021, vol. 116]
[3]Singh; Gousuddin, Mohammad; Khan, Huma [European Journal of Molecular and Clinical Medicine, 2021, vol. 8, # 2, p. 182 - 200]
[4]Abdel-Aziz, Mohamed; Gomaa, Hesham A. M.; Hassan, Heba A.; Hayallah, Alaa M.; Hisham, Mohamed; Youssif, Bahaa G. M. [Journal of Molecular Structure, 2022, vol. 1254]

40
[ 99-03-6 ]
[ 123-11-5 ]
[ 952578-02-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With ethanol; sodium hydroxide at 20℃; for 3h;
62.5%	With sodium hydroxide In ethanol at 20℃;	3 Method 1 General procedure: An acetophenone derivative (1 equivalent), a benzaldehyde derivative (1 equivalent), and NaOH (1 equivalent) were added to an ethanol solvent and stirring was performed at room temperature. Water was added to the reaction mixture and extraction with ethyl acetate was performed. The organic solvent layer was collected and washed once again with water. Anhydrous MgSO4 was added thereto and dehydration was performed. Then, the solvent was distilled off under reduced pressure, and the remaining residue was purified by silica gel chromatography, to prepare the compound.
62%	With sodium hydroxide In ethanol at 20℃;	Synthesis General procedure: Reagents and solvents were purchased from Merck. Series of 17 chalcones was synthesized by Claisen-Schmidt aldol condensation, according to protocol reported by Santos and coauthors with minor modifications [15]. Reactions were carried out at room temperature using 5.0mmol of respective benzaldehyde derivatives and 5.0mmol of respective aminoacetophenones, which were dissolved in ethanol (50mL). Sodium hydroxide in ethanol (1mol L-1) was added as catalyst solution. Reagents conversion was monitored by thin layer chromatography. Crude products were poured onto ice from distilled and deionized water and filtered. All compounds were purified over silica gel chromatography column eluted with mixtures of hexane and ethyl acetate. Melting point of chalcones was measured on open capillaries on Melt Temperature apparatus MS Tecnopon PFM-II. UV-Vis spectra and chromatograms were obtained in High Performance Liquid Chromatography with Diode Array Detector (HPLC-DAD) Agilent Technologies 1220 Infinity equipment, photodiode array system (Agilent Technologies Model 1260 Infinity) and Agilent Zorbax Eclipse Plus C-18 column (250mm×4.6mm, 5µL) using methanol:water (3:1) as mobile phase (1.0mL/min). NMR spectra were obtained in two spectrometers: Bruker Avance III (600MHz) and Bruker Avance III (400MHz), using deuterated dimethyl sulfoxide (DMSO- d6) as internal reference. Low mass spectrometry by electrospray ionization spectra were performed on Bruker Amazon ESI-IT.

62.5%		P.1.t.o.151 [Production Example 31 (E)-1-(3-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (YE-03) [Production Example 31 (E)-1-(3-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (YE-03) According to Method 1 above, 3-aminoacetophenone (1.00 g, 7.40 mmol), 4-methoxybenzaldehyde (1.00 g, 7.40 mmol) and NaOH (0.30 g, 7.40 mmol) were used as starting materials. The residue was purified by silica gel chromatography (developing solvent: (ethyl acetate/n-hexane = 1:2 → 1:1) to obtain the compound of Production Example 3 (0.83 g, 62.5% yield) as an orange solid. Rf 0.40 (ethyl acetate/n-hexane = 1:1); 1H-NMR (400 MHz, CDCl3) δ 3.83 (br s, 2H), 3.85(s, 3H), 6.88 (ddd, J = 8.0, 2.4, 0.8Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 7.27(dd, J = 8.0, 7.6 Hz, 1H), 7.31 (dd, J = 2.0, 1.6 Hz, 1H), 7.36 (d, J = 15.6 Hz, 1H), 7.38 (ddd, J = 7.6, 1.6, 0.8 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 15.6 Hz, 1H); 13C-NMR(100 MHz, CDCl3) 56.0, 56.3, 112.7, 113.9, 114.1, 116.8, 123.3,125.2, 128.9, 131.3, 138.6, 151.2, 153.4, 153.7, 188.8 ppm.
18.1%	With sodium hydroxide at 5 - 8℃;
	With sodium hydroxide In ethanol; water monomer at 5 - 20℃;
	Alkaline conditions;

Reference： [1]Location in patent: experimental part Karaman, Isa; Gezegen, Hayreddin; Guerdere, M. Burcu; Dingil, Alparslan; Ceylan, Mustafa [Chemistry and biodiversity, 2010, vol. 7, # 2, p. 400 - 408]
[2]Current Patent Assignee: EWHA WOMANS UNIVERSITY; COLLEGE OF MEDICINE POCHON CHA UNIVERSITY; YONSEI UNIVERSITY - EP3626703, 2020, A1 Location in patent: Paragraph 0051; 0055
[3]Garcia, Mayara A.R.; Theodoro, Reinaldo S.; Sardi, Janaina C.O.; Santos, Mariana B.; Ayusso, Gabriela M.; Pavan, Fernando R.; Costa, Alan R.; Santa Cruz, Lucas M.; Rosalen, Pedro L.; Regasini, Luis O. [Bioorganic Chemistry, 2021, vol. 116]
[4]Current Patent Assignee: YONSEI UNIVERSITY; EWHA WOMANS UNIVERSITY; COLLEGE OF MEDICINE POCHON CHA UNIVERSITY - EP3977988, 2022, A1
[5]Location in patent: experimental part Wu, Jianzhang; Li, Jianling; Cai, Yuepiao; Pan, Yong; Ye, Faqing; Zhang, Yali; Zhao, Yunjie; Yang, Shulin; Li, Xiaokun; Liang, Guang [Journal of Medicinal Chemistry, 2011, vol. 54, # 23, p. 8110 - 8123]
[6]Location in patent: experimental part Wu, Jianzhang; Wang, Cong; Cai, Yuepiao; Peng, Jing; Liang, Donglou; Zhao, Yunjie; Yang, Shulin; Li, Xiaokun; Wu, Xiaoping; Liang, Guang [Medicinal Chemistry Research, 2012, vol. 21, # 4, p. 444 - 452]
[7]Abdel-Aziz, Mohamed; Gomaa, Hesham A. M.; Hassan, Heba A.; Hayallah, Alaa M.; Hisham, Mohamed; Youssif, Bahaa G. M. [Journal of Molecular Structure, 2022, vol. 1254]

41
[ 99-03-6 ]
[ 879-65-2 ]
[ 878609-65-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6773 - 6776

42
[ 851577-69-0 ]
[ 99-03-6 ]
[ 1262861-32-4 ]

Yield	Reaction Conditions	Operation in experiment
74%	With HATU In N,N-dimethyl-formamide at 20℃;	5.1.9. Methyl 3-([5-[(tert-butoxycarbonyl)amino]methyl}-2-methyl-4-(4-methylphenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}amino)benzoate (12a) General procedure: A mixture of compound 10 (500 mg, 1.17 mmol), methyl 3-aminobenzoate (11a) (532 mg, 3.52 mmol) and 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (1.34 g, 3.52 mmol) in N,N-dimethylformamide (DMF) (5 mL) was stirred at room temperature for 16 h. To the reaction mixture was added water, and the mixture was extracted with AcOEt. The extract was washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/AcOEt = 30:70) to afford 12a (170 mg, 26%) as a pale yellow powder.

Reference： [1]Location in patent: experimental part Miyamoto, Yasufumi; Banno, Yoshihiro; Yamashita, Tohru; Fujimoto, Tatsuhiko; Oi, Satoru; Moritoh, Yusuke; Asakawa, Tomoko; Kataoka, Osamu; Takeuchi, Koji; Suzuki, Nobuhiro; Ikedo, Koji; Kosaka, Takuo; Tsubotani, Shigetoshi; Tani, Akiyoshi; Funami, Miyuki; Amano, Michiko; Yamamoto, Yoshio; Aertgeerts, Kathleen; Yano, Jason; Maezaki, Hironobu [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 1, p. 172 - 185]

43
[ 6344-05-4 ]
[ 99-03-6 ]
[ 1320362-03-5 ]

Yield	Reaction Conditions	Operation in experiment
	With diethylamine In ethanol at 20℃;	General two-step procedure for aryl-OVK General Procedure: An isatin (1 eq.) with the desired substitution pattern or N-alkylation (see general procedure above) was condensed with the desired aryl methyl ketone (1 eq.) using diethylamine (1 eq.) in anhydrous ethanol for 2-48 hours (most reactions were complete after 2-3 h). The condensation product could be precipitated in quantitative yield using pentane and isolated by filtration. Without further purification, it was subjected to a 4:1 mixture of glacial acetic acid with concentrated hydrochloric acid and carefully heated to boiling with a heatgun for 20-30 min. The acidic mixture was diluted tenfold with water and neutralized with sodium hydroxide and sodium bicarbonate, whereby the highly colored OVK products precipitated. After filtration and drying, the crude products were dissolved in a minimal amount of acetone and DCM. The solution was gradually triturated with pentane and any precipitating dark impurities filtered off. The final product either crystallized from this solution or could be obtained by removing the volatiles. In most cases, the product was sufficiently pure without any further effort. If necessary, a small quantity of product could be purified by preparative TLC on 1 mm glass-backed silica gel plates, typically using 3:2 ethyl acetate - pentane as developing solvent and 100% ethyl acetate as eluent.

Reference： [1]Klöck, Cornelius; Jin, Xi; Choi, Kihang; Khosla, Chaitan; Madrid, Peter B.; Spencer, Andrew; Raimundo, Brian C.; Boardman, Paul; Lanza, Guido; Griffin, John H. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 9, p. 2692 - 2696]

44
[ 99-03-6 ]
[ 52780-14-0 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 5863 - 5870

45
[ 99-03-6 ]
[ 5400-78-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 5863 - 5870

46
[ 16013-85-7 ]
[ 99-03-6 ]
[ 1229016-74-3 ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine In methanol at 20 - 30℃; for 5h;	1.1-12 Preparation of 2-(3-acetylphenylamino)-6-chloro-3-nitropyridine To 100 ml of methanol were added 3 g (15.5 mmol) of 2,6-dichloronitropyridine and 2.4 ml (17.1 mmol) of triethylamine and 2.1 g (15.5 mmol) of 3-aminoacetophenone was then added thereto, followed by reaction at room temperature (20 to 30°) for about 5 hours. After the reaction was complete, the reactant was filtered, washed with 20 ml of methanol and then dried under vacuum at about 40° to afford 3.7 g (yield: 82%) of the desired compound. Mass (M+): 292.0 1H-NMR (DMSO-d6): 2.60(s, 3H), 7.05(d, 2H), 7.56(m, 1H), 7.77(d, 2H), 7.87(d, 2H), 8.22(s, 2H), 8.56(d, 1H), 10.23(s, 1H).
82%	With triethylamine In methanol at 20 - 30℃; for 5h;	1.1-12 Example 1-12 Preparation of 2-(3-acetylphenylamino)-6-chloro-3-nitropyridine To 100ml of methanol were added 3g (15.5mmol) of 2,6-dichloronitropyridine and 2.4ml (17.1mmol) of triethylamine and 2.1g (15.5mmol) of 3-aminoacetophenone was then added thereto, followed by reaction at room temperature (20 to 30°C) for about 5 hours. After the reaction was complete, the reactant was filtered, washed with 20ml of methanol and then dried under vacuum at about 40°C to afford 3.7g (yield: 82%) of the desired compound. Mass (M+): 292.0 1H-NMR (DMSO-d6): 2.60(s, 3H), 7.05(d, 2H), 7.56(m, 1H), 7.77(d, 2H), 7.87(d, 2H), 8.22(s, 2H), 8.56(d, 1H), 10.23(s, 1H).

Reference： [1]Current Patent Assignee: DONGWHA PHARM CO.,LTD. - US2011/306606, 2011, A1 Location in patent: Page/Page column 12
[2]Current Patent Assignee: DONGWHA PHARM CO.,LTD. - EP2394993, 2011, A2 Location in patent: Page/Page column 17

47
[ 99-03-6 ]
[ 86-51-1 ]
[ 807642-75-7 ]

Yield	Reaction Conditions	Operation in experiment
57.2%	With sodium hydroxide at 5 - 8℃;
41%	With potassium hydroxide In ethanol at 5 - 20℃;	2 General procedure for the synthesis of aminochalcones (6) General procedure: To a stirred solution of benzaldehyde 4 (5 mmol) and aminoacetophenone 5 (5 mmol) in ethanol (15 mL) at 5 C, then 40% KOH (10 mL) was added dropwise, and stirred at room temperature overnight. The reaction mixture was neutralized with 2 M HCl, and then extracted with ethyl acetate (3 x 30 mL). The combined organic phases were washed with water (25 mL), dried over anhydrous sodium sulfate and evaporated to dryness. The crude product was purified using silica gel column chromatography and eluted with 12% acetone-hexane.
41%	With potassium hydroxide In ethanol at 5 - 20℃;	4.2. General procedure for the synthesis of aminochalcones (6) General procedure: To a stirred solution of benzaldehyde 4 (5 mmol) and aminoacetophenone 5 (5 mmol) in ethanol (15 mL) at 5 °C, then 40% KOH (10 mL) was added dropwise, and stirred at room temperature overnight. The reaction mixture was neutralized with 2 M HCl, and then extracted with ethyl acetate (3 x 30 mL). The combined organic phases were washed with water (25 mL), dried over anhydrous sodium sulfate and evaporated to dryness. The crude product was purified using silica gel column chromatography and eluted with 12% acetone-hexane.

Reference： [1]Location in patent: experimental part Wu, Jianzhang; Li, Jianling; Cai, Yuepiao; Pan, Yong; Ye, Faqing; Zhang, Yali; Zhao, Yunjie; Yang, Shulin; Li, Xiaokun; Liang, Guang [Journal of Medicinal Chemistry, 2011, vol. 54, # 23, p. 8110 - 8123]
[2]Pingaew, Ratchanok; Saekee, Amporn; Mandi, Prasit; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong [European Journal of Medicinal Chemistry, 2014, vol. 85, p. 65 - 76]
[3]Pingaew, Ratchanok; Saekee, Amporn; Mandi, Prasit; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong [European Journal of Medicinal Chemistry, 2014, vol. 85, p. 65 - 75]
[4]Alyafeai, Eman; Fan, Qiyun; Hou, Shengjie; Hu, Yu; Jiang, Liping; Li, Jing; Li, Wulan; Liu, Bo; Liu, Xiaohua; Liu, Yuan; Su, Tiande; Tang, Yaqin; Wu, Jianzhang; Wu, Mengqi; Zheng, Zhiwei [European Journal of Medicinal Chemistry, 2022, vol. 234]

48
[ 110-91-8 ]
[ 99-03-6 ]
[ 1345138-66-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride In water Heating; Stage #2: With sodium nitrite In water at 0℃; for 0.166667h; Stage #3: morpholine Further stages;	2.3. Preparation of 1-{3-[(E)-morpholin-4-yldiazenyl]phenyl}ethanone (1) 1-(3-Aminophenyl)ethanone (3.00 g, 22.2 mmol) was added to 7 mL of 6 M HCl and heated to yield a clear yellow-orange solution, which was cooled to 0 °C to induce the formation of a yellow-orange solid. The solid was maintained at 0 °C and a solution of 1.66 g (24.1 mmol) of NaNO2 in 4 mL of H2O was added dropwise over 10 min, with good stirring of the reaction mixture. A dark amber solution resulted. To this stirred solution, 2.2 mL (2.18 g, 25.0 mmol) of morpholine was added dropwise over 10 min, resulting in the formation of a dark orange precipitate. The mixture was allowed to warm to room temperature and brought to pH 8 with saturated aqueous NaHCO3, which resulted in the formation of a red-orange oil. The aqueous mixture was extracted three times with 40 mL of CH2Cl2. The CH2Cl2 portions were combined, dried with MgSO4 and evaporated to yield 5.03 g (96%) of 1 as a red-orange oil.

Reference： [1]Location in patent: experimental part Sharrett, Zachary; Villalpando, Andrés; Fronczek, Frank R.; Isovitsch, Ralph [Journal of Molecular Structure, 2011, vol. 1005, # 1-3, p. 167 - 171]

49
[ 99-03-6 ]
[ 122-01-0 ]
N-(3-acetylphenyl)-4-chlorobenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.2%	With triethylamine In dichloromethane Cooling with ice;	N-(3-acetylphenyl)-4-chlorobenzamide (3). To a solution of m-Aminoacetophenone (1) (5.0g, 37.0mmol) in anhydrous DCM (150mL) was dropwise added 4-chlorobenzoyl chloride (2) (6.79g, 38.8mmol) in ice bath followed with another portion of Et3N (4.5g, 44.4mmol). The process of the reaction was monitored with TLC and the solvent was removed under reduced pressure after the completion of the reaction. The residue was washed with diluted hydrochloric acid (1M), saturated NaHCO3 solution and finally recrystallized in a mixture of DCM:PE:EA (150mL, 1:2:1) to give compound 3 and was used directly for next step. White solid, 8.5g, yield 84.2%.
	With sodium hydroxide
	With sodium hydroxide at 20℃;

With sodium hydroxide In ethanol at 70 - 80℃; for 0.5h;

Reference： [1]Cao, Xinguang; Li, Rui; Xiong, Huihua; Su, Jinfang; Guo, Changqing; An, Tianqi; Zong, Hong; Zhao, Ruihua [European Journal of Medicinal Chemistry, 2021, vol. 221]
[2]Location in patent: scheme or table Bandgar, Babasaheb P.; Jalde, Shivkumar S.; Korbad, Balaji L.; Patil, Sachin A.; Chavan, Hemant V.; Kinkar, Santosh N.; Adsul, Laxman K.; Shringare, Sadanand N.; Nile, Shivraj H. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, vol. 27, # 2, p. 267 - 274]
[3]Bandgar, Babasaheb P.; Adsul, Laxman K.; Chavan, Hemant V.; Shringare, Sadanand N.; Korbad, Balaji L.; Jalde, Shivkumar S.; Lonikar, Shrikant V.; Nile, Shivraj H.; Shirfule, Amol L. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5649 - 5657]
[4]Bandgar, Babasaheb P.; Kinkar, Santosh N.; Chavan, Hemant V.; Jalde, Shivkumar S.; Shaikh, Rafik U.; Gacche, Rajesh N. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 1, p. 7 - 11]

50
[ 41717-28-6 ]
[ 99-03-6 ]
[ 304889-44-9 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; In N,N-dimethyl-formamide; for 24h;Reflux;	General procedure: A solution of 6 (4.4 mmol) was added to a solution containing 3- or 4-aminobenzophenone or (3- or 4- aminoacetophenone) (4.4 mmol) and triethylamine (1.3 ml, 8.8 mmol)in dry DMF. The reaction mixture was refluxed for 24 h and then cooled to room temperature. DMF and excess triethylamine were evaporated under reduced pressure. The residue was extracted with dichloromethane and water; the organic layer was separated then dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was purified using silica gel column chromatography (dichloromethane/diethylether) in a ratio of (993:7) unless otherwise indicated.

Reference： [1]Archiv der Pharmazie,2012,vol. 345,p. 401 - 406
[2]Letters in drug design and discovery,2015,vol. 12,p. 417 - 429

51
[ 99-03-6 ]
[ 538-75-0 ]
[ 1383815-14-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	With zinc(II) oxide In toluene at 80℃; for 8h;	4.3. General procedure for nano ZnO catalyzed guanylation of amines with carbodiimides listed in Table 2 and Table 3 General procedure: A mixture of amine (1 mmol), carbodiimide (1.1 mmol) and nanocrystalline ZnO (20 mol %, 0.016 g) was stirred in toluene (1 mL) at 80 °C for 8 h (for aromatic and aliphatic primary amines) or at 110 °C for 10 h (for secondary amines). The progress of the reaction was monitored by TLC analysis. At the end of the reaction, the reaction mixture was allowed to cool to room temperature, centrifuged and filtered the supernatant through a sintered funnel. The catalyst was then washed with ethyl acetate, centrifuged and filtered. The combined filtrate was concentrated under reduced pressure, and further purified by column chromatography on neutral alumina using ethyl acetate/hexane as the eluent to afford the desired product in good yields.
53%	With Zn-Al hydrotalcite In toluene at 110℃; for 14h; Sealed tube;

Reference： [1]Location in patent: experimental part Kantam, M. Lakshmi; Priyadarshini; Amal Joseph; Srinivas; Vinu; Klabunde; Nishina, Yuta [Tetrahedron, 2012, vol. 68, # 29, p. 5730 - 5737]
[2]Mannepalli, Lakshmi Kantam; Dupati, Venkanna; Vallabha, Swarna Jaya; Sunkara, V Manorama [Journal of Chemical Sciences, 2013, vol. 125, # 6, p. 1339 - 1345]

52
[ 1395347-62-2 ]
[ 99-03-6 ]
[ 1395347-68-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; sodium t-butanolate; DavePhos In 1,4-dioxane at 100℃; for 8h; Inert atmosphere;	Typical experimental procedure for the preparation of compound 4a: General procedure: In an oven dried, screw-cap vial equipped with a stirring bar were placed 6-bromo-2-cyclopropyl-3-(pyridin-3-ylmethyl) quinazolin-4(3H)-one (3a) (100 mg, 0.28 mmol) dissolved in anhydrous 1, 4-dioxane (2 mL), p-toluidine (90 mg, 0.85 mmol), and NaOtBu (53 mg, 0.56 mmol). The vial was flushed with argon for 10 min, Pd2(dba)3 (2.5 mg, 0.028 mmole) and DavePhos (L3) (1.7 mg, 0.042 mmol) were added. The vial was sealed with a Teflon-lined cap, and placed in a sand bath that was maintained at 100 °C. The reaction was monitored by TLC. Upon completion at 8 h, the mixture was cooled and diluted with CH2Cl2. The mixture was washed with water and the organic layer was separated and dried over anhydrous Na2SO4. The mixture was evaporated under reduced pressure. The crude product was purified by column chromatography, compound was loaded onto a silica column packed in CH2Cl2. Sequential elution with pet-ether, followed by 20% EtOAc in pet-ether afforded compound 4a (100 mg, 93% yield) as white solid.

Reference： [1]Location in patent: experimental part Garlapati, Ramesh; Pottabathini, Narender; Gurram, Venkateshwarlu; Chaudhary, Avinash B.; Chunduri, Venkata Rao; Patro, Balaram [Tetrahedron Letters, 2012, vol. 53, # 38, p. 5162 - 5166]

53
[ 21240-56-2 ]
[ 99-03-6 ]
[ 1401680-18-9 ]

Yield	Reaction Conditions	Operation in experiment
70%		3-Aminoacetophenone 4 (1 mmol) was dissolved in ethanol (15 ml), 1 ml 20% NaOH solution was added to it and stirred for 10 min at room temperature. Then, 3-formyl-9-methylcarbazole 3 (1 mmol) was added and stirring continued for 24 h at room temperature. After completion of reaction (TLC), reaction mixture was poured over crushed ice and stirred. The precipitate obtained was filtered and recrystallized by using methanol to obtain the target compound 8. Yield: 70%; Yellow solid; Mp: 112-116 C; IR (KBr, cm-1): 3415, 3320, 2930, 1656, 1559, 1434, 1204, 1104, 1016, 955, 778; 1H NMR (400 MHz, DMSO-d6, delta in ppm): 3.93 (s, 3H, NCH3), 5.36 (s, 2H, NH2), 7.24 (t, 1H, J = 8.0 Hz, ArH), 7.49-7.90 (m, 5H, ArH), 8.01-8.31 (m, 4H, ArH and CH=CH), 7.75 (d, 1H, J = 15.9 Hz, CH=CH), 8.79 (s, 1H, ArH), 8.86 (s, 1H, ArH); m/z = 327.20 (m+1).

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5649 - 5657

54
[ 99-03-6 ]
[ 563-76-8 ]
[ 1017663-87-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 1-(3-aminophenyl)ethanone With triethylamine In N,N-dimethyl-formamide at 0℃; Stage #2: α-bromopropionyl bromide In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;
80%	With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 3h; Inert atmosphere;	1; 2 N-(3-Acetylphenyl)-2-bromopropionamide To a stirred solution of 3-amino acetophenone (1.0 g, 7.35 mmol) in dimethylformamide (DMF) (10.0 mE) was addedtriethylamine (Et3N) (1.11 g, 11.03 mmol) at 00 C. followed by the slow addition of 2-bromopropionyl bromide (1.75 g, 8.08 mmol). The reaction was stirred at room temperature (rt) under N2 atmosphere for 3 h, diluted with water (50.0 mE) and the precipitated pale brown solid was filtered and dried togive the title product in 80% yield. ‘H NMR (CDC13, 400 MHz): 8.47 (br s, NH), 8.09-8.08 (m, 1H), 7.92 (dd, J=8.0 Hz, J=1.2 Hz, 1H), 7.73 (dd, J=8.0 Hz, J=1.2 Hz, 1H), 7.46 (t, J=8.0 Hz, 1H), 4.60 (q, J=6.8 Hz, 1H), 2.62 (s, 3H), 1.96 (d, J=7.2 Hz, 3H). ‘3C NMR (CDC13, 100 MHz): 198.0, 167.8,137.8, 137.7, 129.5, 124.8, 124.6, 119.5, 44.8, 26.7, 22.7. ESI-MS calcd for C,,H,213rNO2 (M+Na)291.99. found292.0.

Reference： [1]Bicker, Kevin L.; Subramanian, Venkataraman; Chumanevich, Alexander A.; Hofseth, Lorne J.; Thompson, Paul R. [Journal of the American Chemical Society, 2012, vol. 134, # 41, p. 17015 - 17018]
[2]Current Patent Assignee: SCRIPPS RESEARCH - US9347948, 2016, B2 Location in patent: Page/Page column 23; 24; 28; 29; 35

55
[ 2454-37-7 ]
[ 99-03-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With N-chloro-N-(benzenesulfonyl)benzenesulfonamide; triethylamine In chloroform at 20 - 25℃; for 0.25h; Inert atmosphere; chemoselective reaction;	General procedure for oxidation of electron-rich alcohol and ether General procedure: In a 3 neck, 50.0 mL round-bottomed flask arranged with a nitrogen balloon, calcium chloride guard tube, and magnetic stirrer was charged with chloroform 5.0 mL followed by PS-TEMPO, Biotage (0.6 g, 4.38 mol %). The reaction mixture was cooled to 20-25 °C and added NCBSI reagent portion I (0.29 mmol, 0.5 equiv. w. r. t PS-TEMPO) to activate the resin at once under a stream of nitrogen. The reaction mixture was stirred for 2 minutes. The colour change of resin was observed from yellow to dark red indicated the activation of resin. To the reaction mixture, alcohol or ether (13.1 mmol) was added followed by NCBSI reagent portion II (13.1 mmol). After addition, the colour of the resin changes from red to pale yellow which gives a preliminary indication of reaction completion. The reaction was monitored by TLC and confirm with 2,4-DNPH spray. On completion of the reaction, the TEMPO resin mixture was filtered and washed with chloroform. The filtrate was washed with 1% sodium bicarbonate solution, phase-separated, dried over anhyd. Na2SO4 and evaporated under reduced pressure to give the product. The purity of the product was determined by G.C.
83%	With tert.-butylhydroperoxide; Co(0.137)Fe₃O₄(0.863) In water at 80℃; for 5h;
83%	With tert.-butylhydroperoxide In water at 80℃; for 5h;

82%

With calcomenite; potassium hydroxide In toluene for 28h; Reflux;

Reference： [1]Badani, Purav; Chaturbhuj, Ganesh; Ganwir, Prerna; Misal, Balu; Palav, Amey [Tetrahedron Letters, 2021, vol. 73]
[2]Gawande, Manoj B.; Rathi, Anuj; Nogueira, Isabel D.; Ghumman; Bundaleski; Teodoro; Branco, Paula S. [ChemPlusChem, 2012, vol. 77, # 10, p. 865 - 871]
[3]Gawande, Manoj B.; Rathi, Anuj; Nogueira, Isabel D.; Ghumman; Bundaleski; Teodoro; Branco, Paula S. [Collection of Czechoslovak Chemical Communications, 2012, vol. 77, # 10, p. 865 - 871]
[4]Choudhury, Prabhupada; Behera, Pradyota Kumar; Bisoyi, Tanmayee; Sahu, Santosh Kumar; Sahu, Rashmi Ranjan; Prusty, Smruti Ranjita; Stitgen, Abigail; Scanlon, Joseph; Kar, Manoranjan; Rout, Laxmidhar [New Journal of Chemistry, 2021, vol. 45, # 13, p. 5775 - 5779]

56
[ 1449329-22-9 ]
[ 99-03-6 ]
[ 1449329-23-0 ]

Yield	Reaction Conditions	Operation in experiment
66%	With scandium tris(trifluoromethanesulfonate) In toluene at 60℃;
66%	With scandium tris(trifluoromethanesulfonate) In toluene at 60℃; for 48h; Inert atmosphere;
66%	With scandium tris(trifluoromethanesulfonate) In toluene at 60℃; for 14h; Inert atmosphere; Glovebox;	Beuzyl ((1S,2R,3R,4S,58)-5-((3-acetylphenyl)amino)-2-((S)-1 -((tertbuty ldimethylsilyl)oxy) ethyl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(3,3- dimethylureido)-3,4-dihydroxy-3-methylcyclopentyl)carbamate (14): Beuzyl ((1S,2R,3R,4S,58)-5-((3-acetylphenyl)amino)-2-((S)-1 -((tertbuty ldimethylsilyl)oxy) ethyl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(3,3- dimethylureido)-3,4-dihydroxy-3-methylcyclopentyl)carbamate (14): In a nitrogen-filled glove box, a flame-dried 100-mL round-bottomed flask was charged with Se(OTf)3 (0.38 g, 0.77 mmol, 3.0 equiv). The flask was capped with a rubber septum and removed from the glove box. Toluene (20 mL) was added and to the resulting suspension were added aniline 17 (0.35 g, 2.6 nimol, 10.0 equiv) and a toluene solution (1.5 mL) of epoxide 13 (0.20 g, 0.26 mmol, 1.0 equiv). The reaction was heated to 60 °C with vigorous stirring and maintained for 14 h. (Note: increased reaction times led to product decomposition). The reaction was cooled to rt, diluted with 1420 (10 mL) and EtOAc (10 mL), and the resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic extracts were washed with 0.5M HC1(aq.) (2 x 20 mL), saturated NaHCO3(aq.) (15 mL), dried with magnesium sulfate, and concentrated in vacuo. The crude product was purified via flash chromatography (90:10 to 80:20 hexancs:EtOAc) to afford anilino-alcohol 14 as a yellow, viscous oil (0.16 g, 66%) with recovery of the unreacted epoxide 13 (0.04 g, 18%). Analytical data: [cL]D19 -39.3 (c = 0.70, CHC13); ‘H NMR (600 MHz, CDCI3): 8 8.21 (d, .1=6.6Hz, 111), 7.70 (d, J 6.6 Hz, 2H), 7.51 (d, J 7.2 Hz, 211), 7.39 (t, J 7.2 1-Iz, lH), 7.32 (t, J 7.2 Hz, 2H), 7.28-7.22 (m, 811), 7.16 (t, J’ 7.2 Hz, 2H), 7.12 (t, J 7.8 Hz, lH), 6.79 (d, J= 7.8 Hz, 114), 6.13 (s, 111),5.88 (s, 111), 5.39-5.36 (m, 111), 5.36 (s, 114), 5.04 (d, J 12.0 Hz, 111), 5.01 (d, 1= 12.0 Hz,11-I), 4.78 (dd, J= 4.6, 6.6 Hz, 1H), 4.37 (d, J= 10.2 Hz, IH), 4.13 (s, 1H), 3.68 (dd, J= 4.6,3.0 Hz, 1H), 3.48 (d, J- 10.8 Hz, lii), 2.96 (s, 6H), 2.49 (s, 3H), 1.69 (s, 3H), 1.41 (d, Jzt6.6 Hz, 3H), 0.98 (s, 9H), 0.92 (s, 9H), 0.12 (s, 3H), 0.02 (s, 3H); 13C NMR (150 MHz,CDC13): 6 198.7, 158.6, 158.4, 149.5, 137.7, 136.6, 135.6, 135.4, 132.4, 132.0, 129.6, 128.8,128.2, 128.1, 127.8, 127.6, 118.2, 117.0, 112.6, 83.6, 81.0, 70.3, 68,4, 66.9, 66.5, 63.0, 59.3,36.6, 26.7, 26.7, 25.7, 21.2, 19.4, 19.0, 17.7, -4.3, -6.1; LRMS (ESIj Calcd. forC50H70N8Si2+Na, 933,46; Found, 933.35; JR (thin film, cm’) 3361, 2953, 2358, 1716, 1698,1652, 1539, 1488, 1472, 1243, 1041, 829, 701; TLC (80:20 hexanes:EtOAc): Rf 0.35.

66%

With scandium tris(trifluoromethanesulfonate) In toluene at 60℃; for 14h; Inert atmosphere;

General procedure A for the addition of m-acetylaniline to epoxide 11 General procedure: Benzyl ((1S,2R,3R,4S,5S)-5-((3-acetylphenyl)amino)-2-((S)-1-((tert-butyldimethylsilyl)oxy)ethyl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(3,3 dimethyl ureido)-3,4-dihydroxy-3-methylcyclopentyl)carbamate (16): In a nitrogen-filled glove box, a flame-dried 100-mL roundbottomedflask was charged with Sc(OTf)3 (0.38 g, 0.77 mmol, 3.0 equiv). The flask was cappedwith a rubber septum and removed from the glove box. Toluene (20 mL) was added and to theresulting suspension were added m-acetylaniline (0.35 g, 2.6 mmol, 10.0 equiv) and a toluenesolution (1.5 mL) of epoxide 11 (0.20 g, 0.26 mmol, 1.0 equiv). The reaction was heated to 60°C with vigorous stirring and maintained for 14 h. (Note: increased reaction times led to productdecomposition). The reaction was cooled to rt, diluted with H2O (10 mL) and EtOAc (10 mL),and the resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic extractswere washed with 0.5 M HCl(aq.) (2 x 20 mL), saturated NaHCO3(aq.) (15 mL), dried withmagnesium sulfate, and concentrated in vacuo. The crude product was purified via flashchromatography (90:10 to 80:20 hexanes:EtOAc) to afford anilino-alcohol 16 as a yellow,viscous oil (0.16 g, 66%) with recovery of the unreacted epoxide 11 (0.04 g, 18%).

Reference： [1]Malinowski, Justin T.; Sharpe, Robert J.; Johnson, Jeffrey S. [Science, 2013, vol. 340, # 6129, p. 180 - 182]
[2]Sharpe, Robert J.; Malinowski, Justin T.; Johnson, Jeffrey S. [Journal of the American Chemical Society, 2013, vol. 135, # 47, p. 17990 - 17998]
[3]Current Patent Assignee: UNIVERSITY OF NORTH CAROLINA SYSTEM - WO2014/116792, 2014, A1 Location in patent: Page/Page column 48; 49
[4]Sharpe, Robert J.; Malinowski, Justin T.; Sorana, Federico; Luft, J. Christopher; Bowerman, Charles J.; Desimone, Joseph M.; Johnson, Jeffrey S. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 8, p. 1849 - 1857]

57
[ 99-03-6 ]
[ 107-07-3 ]
[ 40673-66-3 ]

Yield	Reaction Conditions	Operation in experiment
68%	With calcium carbonate In water for 7h; Reflux;
68%	With calcium carbonate In water at 120℃; for 7h;
68%	With calcium carbonate; potassium iodide In water at 120℃; for 7h; Reflux;	[N,N-Bis(2-hydroethyl)-3-amino]acetophenone (A) A mixture of 3-aminoacetophenone (47.5 mmol), 2-chloroethanol (240 mmol), and CaCO3 (65 mmol) in water (60 mL) was heated under reflux with vigorous stirring for 7 h. After hot filtering, the unreacted CaCO3 was washed with a few portions of hot water; then, the filtrate was extracted with CH2Cl2 (40 mL 93), dried over anhydrous MgSO4, and concentrated under reduced pressure to afford a yellow oil. The residue was further purified by SiO2 flash column chromatography to give the required diol A. Yield: 68 % of faint yellow liquid.

Reference： [1]Fang, Xianwen; Yang, Bingqin; Cheng, Zhao; Yang, Meipan; Su, Na; Zhou, Lizhen; Zhou, Jia [Archiv der Pharmazie, 2013, vol. 346, # 4, p. 292 - 299]
[2]Fang, Xianwen; Yang, Bingqin; Cheng, Zhao; Zhang, Pengfei; Yang, Meipan [Research on Chemical Intermediates, 2014, vol. 40, # 4, p. 1715 - 1725]
[3]Yang, Meipan; Fang, Xianwen; Li, Shaoni; Yang, Bingqin [Research on Chemical Intermediates, 2015, vol. 41, # 7, p. 4057 - 4066]

58
[ 33252-30-1 ]
[ 99-03-6 ]
[ 1438416-83-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; at 80℃; for 4h;Sealed tube; Inert atmosphere;	General procedure: General Procedure: An oven-dried test tube equippedwith a magnetic stir bar was charged with 2-chloroisonicotinonitrile (69 mg,0.5 mmol), Pd(OAc)2 (2.25 mg, 2 mol%), BINAP (9.38 mg, 3 mol%) , theamine if solid (1.0 mmol), and Cs2CO3 (228 mg, 1.0 mmol).The vessel was then sealed, evacuated, and backfilled with argon (this sequencewas carried out a total of three times). 1,4-dioxane (2.0 mL) and the amine ifliquid (1.0 mmol) via syringe was added successively under an argon atmosphere., and the solution was heated up to 80C for 4 h in an oil bath. The reactionmixture was allowed to cool to r.t. diluted with dichloromethane, and washed once each withwater and brine, dried over Mg2SO4, filtered, andconcentrated in vacuo. The crude product was then purified by silicagelchromatography mixture of pentane and Et2O or mixture of pentane andethyl acetate. The products were characterized by 1H NMR, 13CNMR and LC-MS.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 3233 - 3237

59
[ 99-03-6 ]
[ 79127-41-6 ]

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 67,p. 142 - 151

60
[ 66495-88-3 ]
[ 99-03-6 ]
1-(3-aminophenyl)-3-(3-hydroxy-2-methoxyphenyl)propenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With potassium hydroxide; In ethanol; at 5℃;	General procedure: A mixture of 4-hydroxy-3-methoxybenzaldehyde (1.5 g, 10.0 mmol) and 3’-aminoacetophenone (1.4 g, 10.0 mmol) is dissolved in 15 mL of ethanol and allowed to stir for several min at 5 C (ice bath). 10 mL of a40 % KOH solution in water is added dropwise to the flask over several min. The mixture is then allowed to stir at room temperature for approximately 10h. After the reaction was completed, the reaction mixture was neutralized with adilute HCl. The solution was extracted with anhydrous ether(3 × 10 mL). The organic layer was concentrated and purified bysilica gel column chromatography (CH2Cl2/methanol = 94/6). Yield 35 %;

Reference： [1]Bulletin of the Korean Chemical Society,2013,vol. 34,p. 3923 - 3926

61
[ 2170-03-8 ]
[ 99-03-6 ]
[ 1623012-35-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	In acetone at 20℃; for 2h;	2.2 Synthesis of 4-[(3-Acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid (1) ITA (0.112 g, 1 mmol) dissolved in a 30 mL acetone and it was stirred at ambient temperature and 3-aminoacetophenone (0.135 g, 1 mmol) was added portion wise over 30 mins.The mixture turned into pale yellow slurry. After stirring 1.5 hr, the slurry was filtered.The solid was washed with acetone and dried to give title compound 1. Single crystals weregrown from methanol by the slow evaporation method. Yield: Light orange powder (85%),mp 180-182 °C.
80%	In acetone at 20℃; for 2h;	4-[(3-Acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid(3b) ITA (2) (0.112 g, 1 mmol) was dissolved in acetone(30 mL), and 3-amino acetophenone (0.135 g, 1 mmol)was added in small portions under stirring at room temperatureover time span of 30 min. The mixture becameyellow slurry. Stirring was continued for 1.5 h, after whichthe solution was filtered. The obtained solid was washedwith acetone and dried. The crude product was furtherpurified by recrystallization method, and single crystalswere grown from methanol by the slow evaporationmethod. The product was obtained as a light yellow solidwith 80 % yield. m.p. 180-182 °C; IR (KBr): νmax (cm-1),3282 (OH), 3055 (NH), 2900 (Ar-H), 2634 (aliphatic C-H)1685 (amide C=O), 1591 (C=C). 1H-NMR (400 MHz,DMSO-d6): δ ppm, 2.55 (3H, s, -CH3), 3.35(2H, s, O=CCH2),5.75 (1H, d, JAB = 1.6 Hz, HA), 6.18 (1H, d,JAB = 1.6 Hz, HB), 7.43-8.17 (4H, m, Ar-H), 10.23 (1H,s, NH), 12.55 (1H, s, OH). LCMS (m/z): 248 (M? ? 1).Calcd. for C13H13NO4: C, 63.15; H, 5.30; N, 5.67; Found:C, 63.13; H, 5.32; N, 5.65 %. XRD data: triclinic, P-1,a = 4.9485 (3) A ° , b = 5.3614 (6) A ° , c = 22.457 (2) A ° ,V = 592.77(9) A ° 3, Z = 2.
	In acetone at 20℃; for 2h;	Experimental Itaconic anhydride (0.112 g, 1 mmol) dissolved in a 30 mL acetoneand it was stirred at ambient temperature and 3-aminoacetophenone (0.135 g, 1 mmol) was added portion wise over 30 min.The mixture turned into pale yellow slurry. After stirring 1.5 h, the slurry was filtered. The solid was washed with acetone and dried to give the title compound. Single crystals were grown from methanol by the slow evaporation method. XRD analysis was done using a Bruker SMART APEXII equipped with an X’ calibur CCD area detector diffractometer. The structure was solved by direct method using the program SHELX97 [18] and were refined by least squares technique. The ORTEP diagram and crystal packing are shown in Figs. S1 and S2 (Supporting materials). In the crystal, moleculesare held together by strong N-H-O and O-H-O intermolecular interactions. The crystal data and parameters for structure refinement of the title compound and given in Table S1 (Supporting material). FT-IR spectrum (Fig. 1) was recorded on Shimadzu-FTIR infrared spectrometer and 1H NMR (400 MHz) spectrum was recorded on a Varian 400 spectrometer.1H NMR spectrum wasrecorded on a Varian 400 spectrometer.

Reference： [1]Nayak, Prakash S.; Narayana, Badiadka; Anthal, Sumati; Gupta, Vivek K.; Kant, Rajni; Yathirajan [Molecular Crystals and Liquid Crystals, 2014, vol. 592, # 1, p. 249 - 258]
[2]Nayak, Prakash S.; Narayana; Sarojini; Fernades, Jennifer; Bharath; Madhu [Medicinal Chemistry Research, 2015, vol. 24, # 12, p. 4191 - 4206]
[3]Raju, Rahul; Panicker, C. Yohannan; Nayak, Prakash S.; Narayana; Sarojini; Van Alsenoy; Al-Saadi, Abdulaziz A. [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015, vol. 134, p. 63 - 72]

62
[ 99-03-6 ]
[ 120-14-9 ]
[ 952578-03-9 ]

Yield	Reaction Conditions	Operation in experiment
57%	With potassium hydroxide In ethanol at 5 - 20℃;	1 General procedure for the synthesis of aminochalcones (6) General procedure: To a stirred solution of benzaldehyde 4 (5 mmol) and aminoacetophenone 5 (5 mmol) in ethanol (15 mL) at 5 C, then 40% KOH (10 mL) was added dropwise, and stirred at room temperature overnight. The reaction mixture was neutralized with 2 M HCl, and then extracted with ethyl acetate (3 x 30 mL). The combined organic phases were washed with water (25 mL), dried over anhydrous sodium sulfate and evaporated to dryness. The crude product was purified using silica gel column chromatography and eluted with 12% acetone-hexane.
57%	With potassium hydroxide In ethanol at 5 - 20℃;	4.2. General procedure for the synthesis of aminochalcones (6) General procedure: To a stirred solution of benzaldehyde 4 (5 mmol) and aminoacetophenone 5 (5 mmol) in ethanol (15 mL) at 5 °C, then 40% KOH (10 mL) was added dropwise, and stirred at room temperature overnight. The reaction mixture was neutralized with 2 M HCl, and then extracted with ethyl acetate (3 x 30 mL). The combined organic phases were washed with water (25 mL), dried over anhydrous sodium sulfate and evaporated to dryness. The crude product was purified using silica gel column chromatography and eluted with 12% acetone-hexane.
52%	With lithium hydroxide In methanol Sonication;

	With potassium hydroxide In ethanol; water at 20℃; for 6h;	4.1.i Synthetic route for RapADOcin with FKBD 8 Reaction conditions: i) KOH, H20/EtOH (1/20), RT, 6h; ii) Pd/C (10%), H2, MeOH, RT, 1.5 h; iii) tert-butyl 2-bromoacetate, K2C03, DMF/acetone (1/2), RT, 4h; iv) (+)- DIPCl, THF, -20°C to RT, 5h; v) FKBD 8, benzoyl chloride, DMAP (5%), NEt3, CH2C12, RT, 4h; vi) TFA (10%), CH2C12, RT, 6h; vii) succinic anhydride, DMAP (5%), CH2C12, RT, 3h; viii) allyl bromide, Cs2C03, DMF, RT, 2h; ix) Pd(PPh3)4 (10%), N-methylaniline, THF, RT, 6h.
	With sodium hydroxide In ethanol; water at 20℃; for 6h;	1 (E)-1-(3-aminophenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one (6). To a solution of 3,4-dimethoxybenzaldehyde (5.10 g) and 3-amino acetophenone (4.15 g) mixture in EtOH (20 mL, 95%), NaOH (0.2 g in 2 mL water) was added. The reaction mixture was stirred at RT for 6 h and a slurry of yellow precipitate was formed. The reaction mixture was then diluted with EtOAc (40 mL) and washed with water (30 mL*3). Upon concentrated, the crude product 6 (9.0 g) is pure enough for the next step.
	Alkaline conditions;

Reference： [1]Pingaew, Ratchanok; Saekee, Amporn; Mandi, Prasit; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong [European Journal of Medicinal Chemistry, 2014, vol. 85, p. 65 - 76]
[2]Pingaew, Ratchanok; Saekee, Amporn; Mandi, Prasit; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong [European Journal of Medicinal Chemistry, 2014, vol. 85, p. 65 - 75]
[3]Kraege, Stefanie; Köhler, Sebastian C.; Wiese, Michael [ChemMedChem, 2016, vol. 11, # 21, p. 2422 - 2435]
[4]Current Patent Assignee: THE JOHNS HOPKINS UNIVERSITY - WO2017/136717, 2017, A1 Location in patent: Paragraph 00042
[5]Current Patent Assignee: RAPAFUSYN RES AND DEVELOPMENT; RAPAFUSYN RESEARCH AND DEVELOPMENT; THE JOHNS HOPKINS UNIVERSITY - US2021/94933, 2021, A1 Location in patent: Paragraph 0249-0250
[6]Abdel-Aziz, Mohamed; Gomaa, Hesham A. M.; Hassan, Heba A.; Hayallah, Alaa M.; Hisham, Mohamed; Youssif, Bahaa G. M. [Journal of Molecular Structure, 2022, vol. 1254]

63
[ 99-03-6 ]
[ 5071-61-4 ]
N-(3-acetylphenyl)-5-phenyl-3-pyrazole carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77.6%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In N,N-dimethyl-formamide; for 4 - 10h;Reflux; Inert atmosphere;	A solution of acid 4 (0.09 g, 0.47 mmol) in dry DMF (2 mL) treated sequentially with amine (5a-i, 6a-e and 7a-h; 0.517 mmol)and triethylamine (0.94 mmol) was stirred under a N2 atmosphere for 15 min, later TBTU (0.56 mmol) was added and reaction mixture refluxed for 4-10 h. The reaction mixture was quenched with aq satd NH4Cl solution (10 mL). After 10 min, it was diluted withCHCl3 (2 10 mL) and washed with water (10 mL), NaHCO3 solution(10 mL) and brine (10 mL). The organic layers were dried over anhydrous sodium sulfate, evaporated and the residue purified by column chromatography using 30% ethyl acetate in pet. ether to afford corresponding amides 8a-i, 9a-e and 10a-h.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 6209 - 6219

64
[ 99-03-6 ]
[ 3392-97-0 ]
(E)-1-(3-aminophenyl)-3-(2,6-dimethoxyphenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: 1-(3-aminophenyl)ethanone With sodium hydroxide In ethanol; water at 20℃; for 0.0833333h; Stage #2: 2,6-dimethoxybenzaldehyde at 20℃;	3.1.2. General Procedure for Synthesis of Chalcones General procedure: A 50 mL flask was charged with substituted acetophenone (5 mmol) and a solution of sodium hydroxide (10 mmol) in a 4:1 (v/v) mixture of ethanol/H2O (25 mL), and the resulting mixture was stirred at room temperature for 5 min. A substituted benzaldehyde (5 mmol) was then added to the reaction, and the resulting mixture was stirred at room temperature. The reaction was then monitored byTLC using ethyl acetate/petroleum ether (1:4 or 1:2 v/v) as the solvent system. Upon completion of the reaction, the crude product was filtered off and recrystallized from a mixture of dichloromethane and ethanol or purified by column chromatography over silica gel eluting with a mixture of petroleum ether and ethyl acetate to give the pure product.

Reference： [1]Bai, Xiao-Guang; Xu, Chang-Liang; Zhao, Shuang-Shuang; He, Hong-Wei; Wang, Yu-Cheng; Wang, Ju-Xian [Molecules, 2014, vol. 19, # 11, p. 17256 - 17278]

65
[ 932-16-1 ]
[ 99-03-6 ]
1-(3-(5-acetyl-1-methyl-1H-pyrrol-2-yl)phenyl)ethan-1-one [ No CAS ]

Reference： [1]Chemistry - A European Journal,2014,vol. 20,p. 12754 - 12758

66
[ 24424-99-5 ]
[ 99-03-6 ]
3-tert-butoxycarbonylaminoacetophenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In tetrahydrofuran for 48h;	4.1.1 Tert-butyl (2-acetylphenyl)carbamate (1a) To a mixture of 1-(2-aminophenyl)ethan-1-one (10mmol, 1.35g) in THF (15mL) was added di-tert-butyl dicarbonate (40mmol, 8.72g) and stirred for 48hat room temperature. Then, the mixture was concentrated in vacuo and extracted with ethyl acetate and water. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 5-20% ethyl acetate in petroleum ether) to give 1a (2.2g, 92%) as a white solid.
95%	With sodium carbonate In tetrahydrofuran; water at 20℃; for 12h;	3-t-Butoxycarbonylamino-acetophenone (2) To a solution of 3-aminoacetophenone, 1 (10 g, 74mmol) and sodium carbonate (8 g, 75 mmol) in a solutionof tetrahydrofuran/water (v/v 200/60 mL) were added di-tbutylpyrocarbonate (34 mL, 148 mmol). Reaction mixturewas stirred at room temperature for 12 h and concentratedto near dryness, diluted with water, and extracted withchloroform. The combined organic phase was dried overanhydrous sodium sulfate, filtered, and concentrated underreduced pressure and the residue was purified by columnchromatography eluting with ethyl acetate/hexane (2:8) toprovide compound 2 (16.5 g, 95%); mp 93-94°C; IR (KBr)3335, 1951, 1733, 1674; 1H-NMR (200 MHz, CDCl3)[20] δ7.93 (t, J = 1.8 Hz, 1H), 7.65 (d, J = 7.9 Hz, 1H), 7.61 (d,J = 7.9 Hz, 1H), 7.38 (t, J = 7.9 Hz, 1H), 6.72 (s, 1H), 2.56(s, 3H), 1.53 (s, 9H); MS (FAB) 236 (M++1).
93%	In 1,4-dioxane for 5h; Reflux;	Synthesis of tert-Butyl (3-acetylphenyl)carbamate (17) 1-(3-aminophenyl)ethan-1-one (2.00 g, 14.8 mmol, 1.0 equiv.) and di-tert-butyldicarbonate (3.89 g, 17.8 mmol, 1.2 equiv.) were dissolved in dioxane (20 mL)and refluxed for 5 h. After cooling down to rt the solvent was removed in vacuo.The residue was dissolved in EtOAc (80 mL) and the organic layer washed with1M aqueous HCl solution (aq., 3x 20 mL), NaHCO3 (aq., sat., 1x 20 mL) and brine (1x 20 mL),dried over MgSO4, filtered and concentrated in vacuo. Separation by flash columnchromatography (10% EtOAc/cyclohexane) afforded tert-butyl (3-acetylphenyl)-carbamate 17as a white solid (3.25 g, 93%). The spectroscopic data obtained are in accordance with thosedescribed in the literature.

88.6%	In 1,4-dioxane at 150℃; for 4h;	1.1 Step 1: Preparation of tert-butyl 3-acetylphenylcarbamate (Compound 2) Add in a solution of 1-(3-aminophenyl)ethanone (Compound 1) (8.0 g, 59.3 mmol) in dioxane (100 mL)Boc20 (16.8 g, 77.1 mmol) was added.The resulting reaction solution was reacted at 150° C. for 4 hours and then concentrated under reduced pressure.The residue was subjected to silica gel column chromatography (PE:EA = 8:1 to 4:1) to give the desired product as a white solid.(12.4 g, 88.6% yield).
	With sodium hydroxide In 1,4-dioxane; water at 0 - 20℃; for 12h;	2A-2.1 Step 1. Synthesis of N-Boc-3-aminoacetophenone To a soLution 1-(3-aminophenyL)ethan-1-one (37 mmol, I eq) in mixture 1,4-dioxane water (40 : 20 mL) cooLed to 0 °C, NaOH (2 eq) and di-tert-butyL dicarbonate (1.1 eq) were added. The reaction was carried out at room temperature for 12 hours. Then the reaction mixture was acidified with 3M hydrochloric acid or 2% citric acid and extractedwith ethyL acetate. The organic Layer was dried over anhydrous magnesium suLfate. The pure product was obtained after soLvent evaporation. The preparation of enoLate and cyclic compound was carried out using procedures of ExampLes IA and 2A, respectiveLy.
	In 1,4-dioxane at 20℃;
	In tetrahydrofuran
	In water at 20℃;

Reference： [1]Dou, Xiaodong; Huang, Huixia; Jiang, Lan; Jiao, Ning; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Zhang, Lihe; Zhu, Guiwang [European Journal of Medicinal Chemistry, 2020, vol. 201]
[2]Pratap, Ram; Satyanarayana, Mavurapu; Shukla, Poonam; Srivastava, Arvind K; Tiwari, Priti; Tripathi, Brajendra K [Indian Journal of Heterocyclic Chemistry, 2021, vol. 31, # 3, p. 341 - 345]
[3]Becker, Marc R.; Morack, Tobias; Robertson, Jack; Metternich, Jan B.; Mück-Lichtenfeld, Christian; Daniliuc, Constantin; Burley, Glenn A.; Gilmour, Ryan [Tetrahedron, 2020, vol. 76, # 51]
[4]Current Patent Assignee: PHARMARESOURCES SHANGHAI CO LTD - CN104860890, 2018, B Location in patent: Paragraph 0090; 0092; 0094; 0095
[5]Current Patent Assignee: ADAMED SP. Z.O.O. - WO2015/189799, 2015, A1 Location in patent: Page/Page column 29; 30
[6]Ng, Hui-Li; Chen, Shangying; Chew, Eng-Hui; Chui, Wai-Keung [European Journal of Medicinal Chemistry, 2016, vol. 115, p. 63 - 74]
[7]Xiong, Xiaodong; Yeung, Ying-Yeung [Angewandte Chemie - International Edition, 2016, vol. 55, # 52, p. 16101 - 16105][Angew. Chem., 2016, vol. 128, # 52, p. 16335 - 16339,5]
[8]Jiang, Xipeng; Jiang, Yaqiqi; Liu, Qianqian; Li, Bao; Shi, Da-Qing; Zhao, Yingsheng [Journal of Organic Chemistry, 2022, vol. 87, # 5, p. 3546 - 3554]

67
[ 99-03-6 ]
[ 79-44-7 ]
[ 42865-65-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine; dmap In dichloromethane at 20℃; Sealed tube;	General procedure A General procedure: Anilines (1 mmol), N,N-dimethylcarbamoyl chloride (2 mmol), DMAP (1 mmol), and pyridine (4mmol) were sequentially added under air to a reaction tube equipped with a stir bar and aseptum. CH2Cl2 (2 mL) was added by syringe and the resulting mixture vigorously stirred for36-48 h at ambient temperature. After this time, the contents of the flask were extracted withEtOAc. The solution obtained was filtered through the plug of silica gel and anhydrous MgSO4,and then concentrated by rotary evaporation. The residue was purified by flash chromatography,eluting with hexane/EtOAc to afford the product.

Reference： [1]Nishikata, Takashi; Abela, Alexander R.; Huang, Shenlin; Lipshutz, Bruce H. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1040 - 1064]

68
[ 99-03-6 ]
[ 73035-16-2 ]

Yield	Reaction Conditions	Operation in experiment
32.3%	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h; Inert atmosphere; Stage #2: With sodium hydrogen sulfite; copper(II) sulfate In water at 0℃; for 1h; Inert atmosphere;	1.1 nesulfonyl chloride To a solution of l-(3-aminophenyl)ethanone (4 g, 29.59 mmol,1 eq) in HC1 (12 M, 60.00 mL, 24.33 eq) was added a mixture of NaNCh (4.08 g, 59.19 mmol, 2 eq) in H2O (20 mL) with stirred at 0 °C for 30 min under N2 atmosphere. CuSCL (472.35 mg, 2.96 mmol, 0.1 eq) and NaHSCh (30.80 g, 295.94 mmol,10 eq) were added into the mixture with stirred at 0 °C for 1 h under N2 atmosphere. TLC (PE/ EtOAc = 3/ 1, Rf= 0.6) showed that new point was formed and the start material was consumed completely. The reaction mixture was quenched by addition of H2O (50 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were dried over Na2S04, filtered and concentrated under reduced pressure to yield 3-acetylbenzenesulfonyl chloride (2.2 g, 9.56 mmol, 32.3% yield, 95.0% purity) as a white solid, which was used in the next step without further purification. 'H NMR (400 MHz, DMSO-r/f,) d ppm 8.13 (s,1H), 7.91 (d, J= 8.0 Hz,1H), 7.84 (d, J= 7.6 Hz,1H), 7.49 (t, J= 8.0 Hz,1H), 2.57 (s, 3H).
	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite In water; acetic acid at -15 - 20℃; for 0.5h; Stage #2: With sulfur dioxide; copper dichloride In water; acetic acid at 0 - 20℃; for 2h;	1.a a) 3-aminoacetophenone (1g, 7.4mmol) was dissolved in 5mL of glacial acetic acid and 5mL of concentrated hydrochloric acid, sodium nitrite (0.613g, 8.88mmol) was dissolved in 2mL of water, at -15 deg. C was slowly added to the reaction solution, control the temperature not higher than -5 deg. C, stirred for 30 minutes; cuprous chloride (0.22g, 2.22mmol) was dissolved in 10mL of saturated solution of sulfur dioxide in glacial acetic acid, 0 deg. C stirred for 30 minutes, the solution turned from dark green to blue-green, the temperature was controlled so as not to exceed 0 deg. C, was slowly added to the previous reaction solution, stirred for 2 hours at room temperature, the reaction solution was poured into 100mL ice water, extracted with ethyl acetate (50mL * 2), and the combined organic layer was washed with 100mL water, 100mL saturated chlorine washed with sodium solution, dried over anhydrous sodium sulfate, the organic solvent was distilled off under reduced pressure, the crude product B was used without further purification onto the next step.
	Stage #1: 1-(3-aminophenyl)ethanone With hydrogenchloride; sodium nitrite In water at -5℃; for 0.5h; Stage #2: With sulfur dioxide; acetic acid; copper(l) chloride In water at -5 - 20℃; for 1.33333h;	16.1 Step 1: 3-Acetylbenzenesulfonyl chloride To a stirred solution of l-(3-aminophenyl)ethan-l-one (5.0 g, 37 mmol, 1.00 equiv) in HC1 aq. (6M, 30 mL) was added NaNO2(3.83 g, 55.5 mmol, 1.50 equiv) in H2O (3 mL) dropwise at -5°C. The reaction solution was stirred for 30 min at -5°C. This solution was assigned solution A. Then CuCl (5.49 g, 55.5 mmol, 1.50 equiv) was added to a 250-mL single necked round-bottom flask with AcOH (30 mL) as the solvent, SO2(g) was bubbled to the solution with stirring at 0°C for 20 min, this solution was assigned as solution B. To the solution B was added solution A dropwise with stirring at -5°C. The reaction solution was stirred for additional 1 h at rt. The mixture was added ice/TBO (50 mL) and extracted with DCM (3x200 mL). The combined organic layers were washed with water (3x200 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under vacuum. This resulted in 3.0 g (crude) of the title compound as yellow oil.

Reference： [1]Current Patent Assignee: IKENA ONCOLOGY INC - WO2021/127301, 2021, A1 Location in patent: Paragraph 00221; 00408
[2]Current Patent Assignee: Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - CN105481790, 2016, A Location in patent: Paragraph 0116; 0117; 0118; 0119
[3]Current Patent Assignee: ANOVIA BIOSCIENCES - WO2021/216592, 2021, A1 Location in patent: Paragraph 383-384

69
4-(5-carboxy-1H-pyrazol-3-yl)pyridin-1-ium chloride [ No CAS ]
[ 99-03-6 ]
N-(3-acetylphenyl)-3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: 4-(5-carboxy-1H-pyrazol-3-yl)pyridin-1-ium chloride With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: 1-(3-aminophenyl)ethanone In N,N-dimethyl-formamide at 0 - 20℃; for 24h;	Synthetic procedure for N-(3-acetylphenyl)-3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide(5) The intermediate 4 (1.0g, 5.29mmol) was dissolved in Dimethylformamide (5mL) and carbonyldiimidazole (1.02g, 6.3mmol) was added at 0° C. The reaction mixture was stirred for 30min at room temperature. To the reaction mixture 3-amino acetophenone (0.714g, 5.29mmol) was added at 0°C and again stirred for 24h at ambient temperature. Then the reaction mixture was quenched with crushed ice. The white precipitate 5 obtained was filtered, dried in vacuum and used for further reactions. White solid. Yield 92%. 1H NMR (300MHz, DMSO-D6) δ 14.25 (s, 1H), 10.15 (s, 1H), 8.64 (d, J=4.5Hz, 2H), 8.40 (s, 1H), 8.12 (d, J=7.8Hz, 1H), 7.76 (bs, 2H), 7.70 (d, J=7.4Hz, 1H), 7.50-7.45 (m, 2H), 2.63 (s, 3H). 13C NMR (75MHz, DMSO-D6) δ 196.25, 158.71, 148.91, 150.91, 137.73, 136.13, 127.71, 123.50, 122.32, 118.60, 118.39, 103.13, 25.44. ESI-LC/MS calculated m/z 306.11, found 307.31 (M++1). IR: 3309, 3123, 1681, 1645, 1607, 1554, 818, 771. Anal. Calcd for: C17H14N4O2: C, 66.66; H, 4.61; N, 18.29%. Found: C, 66.62; H, 4.68; N, 18.28%.

Reference： [1]Sribalan, Rajendran; Banuppriya, Govindharasu; Kirubavathi, Maruthan; Jayachitra; Padmini, Vediappen [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 23, p. 5624 - 5630]

70
[ 1593-08-4 ]
[ 99-03-6 ]
(2E)-1-(3-aminophenyl)-3-(quinoxalin-2-yl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		This procedure is based on our previous report27 and vogels procedure36. To a conical flask containing NaOH solution (1.5eq, 10 mL H2O) was added substituted acetophenones (1mmole) in ethanol (10 mL), and the reaction mixture was stirred for 10 minutes to allow enolate formation, to this was added quinoxaline-2- carbaldehyde 1 (1mmole) and the reaction mixture was stirred till completion. After completion of the reaction, as monitored by TLC the reaction mixture was poured in an ice bath and was acidified using conc. HCl. The solid obtained was then filtered, dried and recrystallized using Ethanol. The quinoxalinyl chalcone 2a-n were then characterized using IR, NMR (1H, 13C) and HR-MS spectroscopy. The purity was checked by HPLC measurements using mobile phase consisting methanol and water in the ratio 90:10.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2174 - 2180

71
[ 14452-30-3 ]
[ 99-03-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With acetamidine hydrochloride; caesium carbonate In N,N-dimethyl-formamide at 130℃; for 20h; Inert atmosphere; Green chemistry;	Heterogeneous copper-catalysed synthesis of primary arylamines General procedure: A two-necked flask equipped with a magnetic stirring bar was charged with Cs2CO3 (2 or 3 mmol), MCM-41-L-proline-CuI (0.1 mmol), aryl iodide (1.0 mmol), acetamidine hydrochloride (1.2 or 2 mmol) and DMF (3.0 mL) under Ar. The reaction mixture was stirred at 130 or 140 °C for 20 h. After being cooled to room temperature, the mixture was diluted with CH2Cl2 (10 mL) and filtered. The catalyst was washed with distilled water (2 × 5 mL) and EtOH (2 × 5 mL) and air dried when reused in the next run. The filtrate was concentrated with the aid of a rotary evaporator and the residue was purified by column chromatography on silica gel using petroleum ether (30-60 °C)/ethylacetate (10:1 to 1:1) as eluent to give the desired product 2. All the products 2a-z are known compounds.

Reference： [1]Huang, Xue; Xiao, Ruian; You, Chongren; Yan, Tao; Cai, Mingzhong [Journal of Chemical Research, 2017, vol. 41, # 6, p. 315 - 320]

72
[ 99-03-6 ]
[ 79-22-1 ]
[ 87743-55-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine In acetone for 3h; Reflux;	4.2.2.1. General procedure for the preparation of alkyl (3-/4-acetylphenyl)carbamates (3a-6a). General procedure: A solution of an appropriatealkyl chloroformiate (37 mmol) in acetone (5 mL) was addeddropwise to a stirred solution of 3-aminoacetophenone (5.00 g;37 mmol) or 4-aminoacetophenone (5.00 g; 37 mmol) and pyridine(3.0 mL; 37 mmol) in acetone (20 mL), and then the mixture washeated to reflux for 3 h. The solvent was removed at reducedpressure, and the resulting solid was washed with water, andrecrystallized from EtOH.
95%	With pyridine In acetone for 3h; Reflux;	3.2.1. General Procedure For the Preparation of Alkyl (3-/4-Acetylphenyl)carbamates (3a-h) General procedure: Into a stirred solution of 3-aminoacetophenone 1a (CAS Registry Number 99-03-6; 5.00 g, 37 mmol)or 4-aminoacetophenone 1b (CAS Registry Number 99-92-3; 5.00 g, 37 mmol) and pyridine (3.0 mL,37 mmol) in 20 mL of acetone, a solution of methyl chloroformate 2a (CAS Registry Number 79-22-1;3.5 mL, 37 mmol), ethyl chloroformate 2b (CAS Registry Number 541-41-3; 4.0 mL, 37 mmol), propylchloroformate 2c (CAS Registry Number 109-61-5; 4.5 mL, 37 mmol) or butyl chloroformate 2d (CASRegistry Number 592-34-7; 5.0 mL, 37 mmol) in 5 mL of acetone, was added dropwise. The particularmixture was heated to reflux for 3 h [28]. When the reaction was completed (TLC control), the solventswere removed in vacuo, crude solid products 3a-h were washed with distilled water and recrystallizedfrom absolute ethanol. Full characterization data for the compounds 3a-h (Scheme 1), isolated ascolourless solids, are given below.Methyl (3-acetylphenyl)carbamate (3a); CAS Registry Number 87743-55-3). Yield 6.80 g (95%); Mr 193.19;Mp 103-104 °C; 1H-NMR (DMSO-d6) δH (ppm): 9.87 (s, 1H, NHCOO), 8.06 (s, 1H, Ar-H), 7.71 (d,1H, Ar-H, J = 7.7 Hz), 7.61 (d, 1H, Ar-H, J = 7.3 Hz), 7.44 (t, 1H, Ar-H, J = 8.2 Hz), 3.69 (s, 3H,COOCH3), 2.55 (s, 3H, COCH3); 13C-NMR (DMSO-d6) δC (ppm): 197.47, 153.92, 139.49, 137.37, 129.01,122.56, 122.36, 117.26, 51.53, 26.51. HR-MS: for C10H11O3N [M - H]+ calculated 192.06552 m/z, found

Reference： [1]Vettorazzi, Marcela; Angelina, Emilio; Lima, Santiago; Gonec, Tomas; Otevrel, Jan; Marvanova, Pavlina; Padrtova, Tereza; Mokry, Petr; Bobal, Pavel; Acosta, Lina M.; Palma, Alirio; Cobo, Justo; Bobalova, Janette; Csollei, Jozef; Malik, Ivan; Alvarez, Sergio; Spiegel, Sarah; Jampilek, Josef; Enriz, Ricardo D. [European Journal of Medicinal Chemistry, 2017, vol. 139, p. 461 - 481]
[2]Gonec, Tomás; Malík, Ivan; Csöllei, Jozef; Jampílek, Josef; Stolaríková, Jirina; Solovic, Ivan; Miku, Peter; Keltoová, Stanislava; Kollár, Peter; O'Mahony, Jim; Coffey, Aidan [Molecules, 2017, vol. 22, # 12]

73
[ 53250-83-2 ]
[ 99-03-6 ]
N-(3-acetylphenyl)-2-chloro-4-methanesulfonylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96.2%		In a 50 ml round bottom flask, add2-Chloro-4-methylsulfonylbenzoic acid(0.71 g, 3.0 mmol)In dichloromethane (30 ml), thionyl chloride (1 ml, 12 mmol) was added dropwise at room temperature,And drop 6 dropsN, N-dimethylformamide, heated to reflux,Reaction for 6 hours. Spin to remove excess thionyl chloride and methylene chloride,Tetrahydrofuran was added(20 ml) was dissolved,Add dropwise at room temperatureM-Aminoacetophenone (0.40 g, 3.0 mmol)In tetrahydrofuran (20 ml)Triethylamine (700 mul, 5.0 mmol) was added dropwise and the reaction was carried out at room temperature for 6 hours. After the reaction was concentrated by evaporation, washed with water, extracted with ethyl acetate,After drying, the residue was purified by column chromatography to give 1.02 g of N- (3-phenylacetyl) -2-chloro-4-methylsulfonylbenzamide (III) in 96.2percent yield

Reference： [1]Patent: CN106892863,2017,A .Location in patent: Paragraph 0055; 0056; 0057; 0058

74
[ 110-91-8 ]
[ 99-03-6 ]
[ 5425-46-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With sulfur In neat (no solvent) at 100℃; for 0.75h; Green chemistry;	General procedure for the Willgerodt-Kindler reaction General procedure: To a mixture of ketone (2 mmol), sulfur (2.4 mmol), and secondary amines (2.4 mmol) sulfated polyborate(10 wt%) was added. The mixture was heated at 100 °C in an oil bath. The reaction was monitored by thin-layer chromatography. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate (3 9 5 mL) and the catalyst was removed by filtration. The combined organic layers were washed with water, dried over sodium sulfate and evaporated under reduced pressure to afford crude products, which were purified by column chromatography using petroleum ether and ethyl acetate solvent system. The products obtained were known compounds and were identified by 1H NMR spectroscopy. The spectral data were compared with those in the literature.

Reference： [1]Rekunge, Deelip S.; Khatri, Chetan K.; Chaturbhuj, Ganesh U. [Monatshefte fur Chemie, 2017, vol. 148, # 12, p. 2091 - 2095]

75
[ 99-03-6 ]
[ 109-61-5 ]
propyl (3-acetylphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine In acetone for 3h; Reflux;	3.2.1. General Procedure For the Preparation of Alkyl (3-/4-Acetylphenyl)carbamates (3a-h) General procedure: Into a stirred solution of 3-aminoacetophenone 1a (CAS Registry Number 99-03-6; 5.00 g, 37 mmol)or 4-aminoacetophenone 1b (CAS Registry Number 99-92-3; 5.00 g, 37 mmol) and pyridine (3.0 mL,37 mmol) in 20 mL of acetone, a solution of methyl chloroformate 2a (CAS Registry Number 79-22-1;3.5 mL, 37 mmol), ethyl chloroformate 2b (CAS Registry Number 541-41-3; 4.0 mL, 37 mmol), propylchloroformate 2c (CAS Registry Number 109-61-5; 4.5 mL, 37 mmol) or butyl chloroformate 2d (CASRegistry Number 592-34-7; 5.0 mL, 37 mmol) in 5 mL of acetone, was added dropwise. The particularmixture was heated to reflux for 3 h [28]. When the reaction was completed (TLC control), the solventswere removed in vacuo, crude solid products 3a-h were washed with distilled water and recrystallizedfrom absolute ethanol. Full characterization data for the compounds 3a-h (Scheme 1), isolated ascolourless solids, are given below.
83%	With pyridine In acetone for 3h; Reflux;	4.3.1. General procedure for the preparation of alkyl (2-/3-acetylphenyl)carbamates (14a-21a) General procedure: A solution of an appropriate alkyl chloroformiate (37 mmol) inacetone (5 mL) was added dropwise to a stirred solution of 2-aminoacetophenone(5.00 g; 37 mmol) or 3-aminoacetophenone (5.00 g;37 mmol) and pyridine (3.0 mL; 37 mmol) in acetone (20 mL), and thenthe mixture was heated to reflux for 3 h. The solvent was removed atreduced pressure, and the resulting solid was washed with water, andrecrystallized from EtOH.

Reference： [1]Gonec, Tomás; Malík, Ivan; Csöllei, Jozef; Jampílek, Josef; Stolaríková, Jirina; Solovic, Ivan; Miku, Peter; Keltoová, Stanislava; Kollár, Peter; O'Mahony, Jim; Coffey, Aidan [Molecules, 2017, vol. 22, # 12]
[2]Campos, Ludmila E.; Garibotto, Francisco M.; Angelina, Emilio; Kos, Jiri; Tomašič, Tihomir; Zidar, Nace; Kikelj, Danijel; Gonec; Marvanova, Pavlina; Mokry, Petr; Jampilek; Alvarez, Sergio E.; Enriz, Ricardo D. [Bioorganic Chemistry, 2019, vol. 91]

76
[ 51757-37-0 ]
[ 99-03-6 ]
4-({4-[(3-acetylphenyl)amino]-6-chloro-1,3,5-triazin-2-yl} amino)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97.1%	Stage #1: 4-(4',6'-dichloro-1',3',5'-triazin-2'-ylamino)-benzene-sulfonamide With potassium carbonate In N,N-dimethyl-formamide for 0.166667h; Stage #2: 1-(3-aminophenyl)ethanone In N,N-dimethyl-formamide at 35℃;	12 4.5. General method for synthesis of disubstituted derivatives ofcyanuric chloride (4 - 16) General procedure: One equivalent (eq) of starting dichlorotriazinyl benzenesulfonamide(1, 2 or 3) [3] was dissolved in DMF as a solvent. Then 1 eq of solid anhydrous potassium carbonate was added in portions. After 10 min of stirring 1 eq of the appropriate nucleophile was addedalso in portions. Reaction was stirred at 35°C until disappearance of starting material (monitored by TLC: CH3OH was used as eluent,detection with UV light and ninhydrin). After completion of the reaction was crushed ice added to the reaction mixture and the precipitate formed was collected by filtration. Purification of a crude product was made by its solution in acetone and pure product was precipitated by addition of isopropyl alcohol.

Reference： [1]Havránková, Eva; Csöllei, Jozef; Vullo, Daniela; Garaj, Vladimír; Pazdera, Pavel; Supuran, Claudiu T. [Bioorganic Chemistry, 2018, vol. 77, p. 25 - 37]

77
[ 99-03-6 ]
[ 149914-98-7 ]

Yield	Reaction Conditions	Operation in experiment
94.71%	With N-Bromosuccinimide In d<SUB>7</SUB>-N,N-dimethylformamide at 25℃; for 2h;	24.1 24.1 Preparation of 1-(5-amino-2-bromo-phenyl)ethanone A solution of 1-(3-aminophenyl)ethanone (10.0 g, 74.0 mmol, 1 eq) in DMF (70 mL) was dropwise a solution of NBS (13.2 g, 74.0 mmol, 1 eq) in DMF (70 mL) at 25°C over a period of 1 h, the resulting mixture was stirred at 25°C for 1 h. The reaction mixture was poured into H2O (100 mL), and the aqueous phase was extracted with EtOAc (40 mL x 3). The combined organic layers were washed with sat. aq. NaHCO3 (20 mL x 3), H2O (15 mL x 3) and brine (10 mL x 3), dried over Na2SO4, filtered and concentrated in vacuo to give 1-(5-amino-2-bromo- phenyl)ethanone (15.0 g, 70.1 mmol, 94.71% yield) was as brown oil.1H NMR (CDCl3, 400 MHz) d 7.34 (d, J = 8.4 Hz, 1H), 6.75 (d, J = 2.8 Hz, 1H), 6.62 (dd, J = 8.8, 2.8 Hz, 1H), 3.82 (br s, 2H).
81%	With N-Bromosuccinimide In N,N-dimethyl-formamide	a a. 2’-Bromo-5’-amino-acetophenone To a solution of 3’-aminoacetophenone (2.0 g, 1.48 mmol) in 15 mL anhydrous DMF was added dropwise a 15 mL DMF solution of freshly recrystallized N-bromosuccinimide (2.63 g, 1.48 mmol). The reaction was monitored by LC/MS and the addition ofNBS solution was stopped once the starting material was consumed. The reaction was diluted 10-fold with EtOAcand washed 3 times with saturated NaHCO3 solution, followed by a wash with brine. Theorganic phase was dried over Na2 SO4 and concentrated to crude oil. The product was purified onsilica gel flash column chromatography using a gradient of 5 - 70% EtOAc in hexanes to give2.56 g white crystalline solid (8 1%). ‘H NMR (500 IVIHz, d6-DMSO) 7.25 (d, J 8.6 Hz, 1),6.74 (s, 1), 6.63 - 6.55 (m, 1), 5.50 (s, 2), 2.51 (s, 3). LC/MS (ESI) m/z: [M+H] 214.0, 216.0.
81.1%	With N-Bromosuccinimide In N,N-dimethyl-formamide

Reference： [1]Current Patent Assignee: BORAGEN; BORAH - WO2021/3501, 2021, A1 Location in patent: Paragraph 0394-0396
[2]Current Patent Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY - WO2019/46465, 2019, A2 Location in patent: Page/Page column 27
[3]Ahn, Yong-Mo; Alland, David; Awasthi, Divya; Capodagli, Glenn C.; Connell, Nancy; Freundlich, Joel S.; Grady, Courtney; Ho Liang, Hsin Pin; Inoyama, Daigo; Jadhav, Ravindra; Kumar, Pradeep; Li, Liping; Li, Shao-Gang; Mina, Marizel; Neiditch, Matthew B.; Park, Steven; Perlin, David S.; Richmann, Todd; Russo, Riccardo; Shrestha, Riju; Sukheja, Paridhi; Tsotetsi, Kholiswa; Wang, Xin; Zimmerman, Matthew; Dartois, Véronique [Cell Chemical Biology, 2020, vol. 27, # 5, p. 560 - 570]

78
[ 99-03-6 ]
[ 131747-42-7 ]
N-(3-acetylphenyl)-6-(trifluoromethyl)picolinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	To a solution of 6- (trifluoromethyl)picolinic acid (4.08 g, 20.7 mmol) in 25 mL of A' L'-di methylformam ide was added HATU (8.7g, 21.8 mmol) an d A', A'-d i i s o p ro p y 1 c t h y 1 am i n c (8.5 mL, 49 mmol). The mixture turned yellow in color and was continued to stir for 10-15 min, then 3'- aminoacetophenone (3.0 g, 21.8 mmol) was added and stirred at rt under a nitrogen atmosphere overnight. The mixture was partitioned between water and EtOAc, the separated organic layer was washed with water, dried, filtered through a pad of silica gel, concentrated, then purified on S1O2 (20-70% EtO Ac/Hexanes) to give the title compound (6.2, 96%) as an off-white solid.

Reference： [1]Patent: WO2019/148005,2019,A1 .Location in patent: Paragraph 1850

79
[ 4397-53-9 ]
[ 99-03-6 ]
3'-amino-4-benzyloxychalcone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.2%	With sodium hydroxide In 1,4-dioxane; methanol at 20℃;	3.3.1. Method I (Compounds 1-6, 10-18) General procedure: In a round bottomed flask 0.24 g (6.00 mmol) of sodium hydroxide was dissolved in 10 mLmethanol and 10 mL dioxane. After that, an appropriate aminoacetophenone (3.67 mmol) and thecorresponding benzaldehyde (3.67 mmol) were added. Reactions were performed in room temperatureon a magnetic stirrer until complete conversion of the substrates. After that, the reaction mixtureswere poured into ice water. Precipitated crystals were collected and purified by liquid columnchromatography on silica gel using mixtures of hexane-acetone, hexane-ethyl acetate or hexane-ethylacetate-methylene chloride as eluents. Compounds 4 and 6 were synthesized at 2.5 times smaller scale.

Reference： [1]Kozłowska, Joanna; Potaniec, Bartłomiej; Baczyńska, Dagmara; Zarowska, Barbara; Anioł, Mirosław [Molecules, 2019, vol. 24, # 22]

80
[ 99-03-6 ]
[ 109-76-2 ]
[ 15889-32-4 ]

Yield	Reaction Conditions	Operation in experiment
49.5%	With oxygen; copper(II) bis(trifluoromethanesulfonate); toluene-4-sulfonic acid; In ethanol; at 80℃; for 72h;	Weigh m-aminoacetophenone (100.0mg, 0.74mmol) in ethanol (3mL),Cu (OTf) 2 (26.8mg, 0.074mmol), TsOH · H2O (84.4mg, 0.44mmol), 1,3-propanediamine (185muL, 2.22mmol) were added in this order,Ventilation and oxygen, heating to 80 C for 72h.After the reaction was completed, the reaction solution was cooled to room temperature, and concentrated by rotary evaporation. Ethyl acetate, water, and saturated sodium carbonate were added to make the mixture alkaline.Extract with ethyl acetate (25 mL x 3), wash with saturated brine (30 mL x 2), and dry over anhydrous sodium sulfate.Column chromatography (EA: PE 1: 3) yielded 62.3 mg of the product with a yield of 49.5%.

Reference： [1]Patent: CN110590649,2019,A .Location in patent: Paragraph 0068-0073

81
[ 487-89-8 ]
[ 99-03-6 ]
(E)-1-(3-aminophenyl)-3-(1H-indol-3-yl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With piperidine In ethanol at 70℃;	2.2. Synthesis of indole chalcone derivatives General procedure: In an RB flask, 1H-indole-3-carboxaldehyde (1 mmol) andappropriate acetophenones (1.2 mmol) were taken and 5 ml ofethanol and 5 drops of piperidine were added. The resulting solutionwas then refluxed at 70 °C and TLC was used to track the reactionprogress. Upon accomplishement of the reaction, thereaction mixture was transferred into cold water and furtherneutralized utilizing 1 N hydrochloric acid. The crude precipitateformed was filtered out, dried and recrystallized from chloroform.All the indole chalcones (1 to 25) were characterized using spectraltechniques and the spectral data are listed in the supplementarydata.

Reference： [1]Joji, Annu; Kannan, Tharanikkarasu; Mani, Maheswaran; Ramesh, Deepthi; Sethumadhavan, Aiswarya; Vijayakumar, Balaji Gowrivel [European Journal of Medicinal Chemistry, 2020, vol. 198]

82
[ 120-57-0 ]
[ 99-03-6 ]
(E)-1-(3-aminophenyl)-3-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydroxide In ethanol; water at 20℃; for 5h;	Synthesis of (E)-1-(3-Aminophenyl)-3-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-one (3c) A round bottom flask was charged with 3-aminoacetophenone (270.3 mg, 2.0 mmol), 2 (300.3mg, 2.0 mmol), ethanol (95%, 1.0 mL), and sodium hydroxide solution (10% w/w in H2O, 1.0 mL). Themixture was stirred at room temperature for 5 h. The mixture was washed with ethanol (100 mL) andfiltered under vacuum. The crude product was purified by column chromatography (SiO2;EtOAc/hexane 1:1) to afford the product as a yellow powder (240.2 mg, 80%). 1H NMR (300 MHz,CDCl3) δ 7.73 (d, J = 15.6 Hz, 1H), 7.39 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.37-7.27 (m, 3H), 7.18-7.10 (m,2H), 6.90 (ddd, J = 7.9, 2.5, 1.1 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.04 (s, 2H), 3.85 (s, 2H); 13C NMR (101MHz, CDCl3) δ 190.7, 150.01, 148.6, 147.0, 144.5, 139.7, 129.6, 129.6, 125.3, 120.6, 119.5, 118.9, 114.6,108.8, 106.8, 101.8; LRMS (ES+) m/z: 268.10 [M + H]+; HRMS (ES+) m/z: calcd. C16H14NO3 [M + H]+ =268.0974; observed 268.0974 (0.0 ppm).

Reference： [1]Cornelio, Marinonio L.; Jones, Alan M.; Le Duff, Cécile S.; Povinelli, Ana Paula R.; Tang, Bridget; Zazeri, Gabriel [Molecules, 2020, vol. 25, # 12]

83
[ 27430-38-2 ]
[ 99-03-6 ]
N'-(1-(3-aminophenyl)ethylidene)-3-((4-methoxyphenyl)amino)propanehydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With acetic acid In methanol at 95℃; for 24h;	3.2.6. General Procedure for the Synthesis of Compounds 28-37 General procedure: To propanehydrazide 1 (0.63 g, 3 mmol) dissolved in methanol (20 mL), corresponding acetophenone (3 mmol) and acetic acid (4 drops; in the case of compounds 29, 30, 32, 33, and 36) were added. The reaction mixture was heated at 95 °C for 4-24 h. Precipitate formed was filtered off, washed with water, and recrystallized from methanol.

Reference： [1]Jonuškienė, Ilona; Kantminienė, Kristina; Klevinskas, Arnas; Mickevičius, Vytautas; Petrikaitė, Vilma; Tumosienė, Ingrida [Molecules, 2020, vol. 25, # 13]

84
[ 89-98-5 ]
[ 99-03-6 ]
(2E)‑1‑(3-aminophenyl)‑3‑(2‑chlorophenyl)prop‑2‑en‑1‑one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydrogenchloride In methanol; water at 120℃;	(2E)-1-(3-Aminophenyl)-3-(2-bromophenyl)prop-2-en-1-one (37) General procedure: 3'-Aminoacetophenone (0.50 g, 3.70 mmol) and 2-bromobenzaldehyde (0.68 g, 3.70 mmol) were suspended in MeOH (4 mL) and HCl (32 wt.% in H2O, FCC, 6 mL). The subsequent reaction mixture was mechanically stirred at 120 °C under reflux while being continuously monitored by TLC. Upon completion, the reaction mixture was cooled to room temperature, ice (15 g) was added and the resulting precipitate was filtered, dried (30 °C) and recrystallized from a suitable solvent to yield the title compound 37 as dark brown powder (1.10 g, 99%).
	Alkaline conditions;

Reference： [1]Janse van Rensburg, Helena D.; Legoabe, Lesetja J.; Terre’Blanche, Gisella [Chemical Papers, 2021, vol. 75, # 4, p. 1581 - 1605]
[2]Abdel-Aziz, Mohamed; Gomaa, Hesham A. M.; Hassan, Heba A.; Hayallah, Alaa M.; Hisham, Mohamed; Youssif, Bahaa G. M. [Journal of Molecular Structure, 2022, vol. 1254]

85
[ 104-88-1 ]
[ 99-03-6 ]
(E)-1-(3′-aminophenyl)-3-(4-chlorophenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydroxide In ethanol at 20℃;	Synthesis General procedure: Reagents and solvents were purchased from Merck. Series of 17 chalcones was synthesized by Claisen-Schmidt aldol condensation, according to protocol reported by Santos and coauthors with minor modifications [15]. Reactions were carried out at room temperature using 5.0mmol of respective benzaldehyde derivatives and 5.0mmol of respective aminoacetophenones, which were dissolved in ethanol (50mL). Sodium hydroxide in ethanol (1mol L-1) was added as catalyst solution. Reagents conversion was monitored by thin layer chromatography. Crude products were poured onto ice from distilled and deionized water and filtered. All compounds were purified over silica gel chromatography column eluted with mixtures of hexane and ethyl acetate. Melting point of chalcones was measured on open capillaries on Melt Temperature apparatus MS Tecnopon PFM-II. UV-Vis spectra and chromatograms were obtained in High Performance Liquid Chromatography with Diode Array Detector (HPLC-DAD) Agilent Technologies 1220 Infinity equipment, photodiode array system (Agilent Technologies Model 1260 Infinity) and Agilent Zorbax Eclipse Plus C-18 column (250mm×4.6mm, 5µL) using methanol:water (3:1) as mobile phase (1.0mL/min). NMR spectra were obtained in two spectrometers: Bruker Avance III (600MHz) and Bruker Avance III (400MHz), using deuterated dimethyl sulfoxide (DMSO- d6) as internal reference. Low mass spectrometry by electrospray ionization spectra were performed on Bruker Amazon ESI-IT.
	Alkaline conditions;

Reference： [1]Garcia, Mayara A.R.; Theodoro, Reinaldo S.; Sardi, Janaina C.O.; Santos, Mariana B.; Ayusso, Gabriela M.; Pavan, Fernando R.; Costa, Alan R.; Santa Cruz, Lucas M.; Rosalen, Pedro L.; Regasini, Luis O. [Bioorganic Chemistry, 2021, vol. 116]
[2]Abdel-Aziz, Mohamed; Gomaa, Hesham A. M.; Hassan, Heba A.; Hayallah, Alaa M.; Hisham, Mohamed; Youssif, Bahaa G. M. [Journal of Molecular Structure, 2022, vol. 1254]

86
[ 99-03-6 ]
[ 1122-91-4 ]
(E)-1-(3′-aminophenyl)-3-(4-bromophenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydroxide In ethanol at 20℃;	Synthesis General procedure: Reagents and solvents were purchased from Merck. Series of 17 chalcones was synthesized by Claisen-Schmidt aldol condensation, according to protocol reported by Santos and coauthors with minor modifications [15]. Reactions were carried out at room temperature using 5.0mmol of respective benzaldehyde derivatives and 5.0mmol of respective aminoacetophenones, which were dissolved in ethanol (50mL). Sodium hydroxide in ethanol (1mol L-1) was added as catalyst solution. Reagents conversion was monitored by thin layer chromatography. Crude products were poured onto ice from distilled and deionized water and filtered. All compounds were purified over silica gel chromatography column eluted with mixtures of hexane and ethyl acetate. Melting point of chalcones was measured on open capillaries on Melt Temperature apparatus MS Tecnopon PFM-II. UV-Vis spectra and chromatograms were obtained in High Performance Liquid Chromatography with Diode Array Detector (HPLC-DAD) Agilent Technologies 1220 Infinity equipment, photodiode array system (Agilent Technologies Model 1260 Infinity) and Agilent Zorbax Eclipse Plus C-18 column (250mm×4.6mm, 5µL) using methanol:water (3:1) as mobile phase (1.0mL/min). NMR spectra were obtained in two spectrometers: Bruker Avance III (600MHz) and Bruker Avance III (400MHz), using deuterated dimethyl sulfoxide (DMSO- d6) as internal reference. Low mass spectrometry by electrospray ionization spectra were performed on Bruker Amazon ESI-IT.
	Alkaline conditions;

Reference： [1]Garcia, Mayara A.R.; Theodoro, Reinaldo S.; Sardi, Janaina C.O.; Santos, Mariana B.; Ayusso, Gabriela M.; Pavan, Fernando R.; Costa, Alan R.; Santa Cruz, Lucas M.; Rosalen, Pedro L.; Regasini, Luis O. [Bioorganic Chemistry, 2021, vol. 116]
[2]Abdel-Aziz, Mohamed; Gomaa, Hesham A. M.; Hassan, Heba A.; Hayallah, Alaa M.; Hisham, Mohamed; Youssif, Bahaa G. M. [Journal of Molecular Structure, 2022, vol. 1254]

87
[ 99-03-6 ]
[ 54865-01-9 ]
3-[(3-acetylphenyl)amino]-5-chloro-4H-1,2,6-thiadiazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: 1-(3-aminophenyl)ethanone; 3,5-dichloro-4H-1,2,6-thiadiazin-4-one In ethanol at 20℃; for 0.5h; Stage #2: With 2,6-dimethylpyridine In ethanol at 20℃; for 2h;	3-[(3-Acetylphenyl)amino]-5-chloro-4H-1,2,6-thiadiazin-4-one (6) (General procedure). To astirred solution of 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (2) (366 mg, 2 mmol) in EtOH (4mL), at ca. 20 °C was added 1-(3-aminophenyl)ethan-1-one (135 mg, 1 mmol) in one portionand the mixture stirred for 30 min at this temperature. Then, 2,6-lutidine (233 μL, 4mmol) was added and the mixture was stirred at this temperature until complete consumptionof the starting material (TLC, 2 h). The yellow solid formed was then filteredunder vacuum and washed with EtOH (2 mL), t-BuOMe (5 mL), and n-hexane (5 mL) togive the title compound 6 (190 mg, 67%) as yellow needles, mp 201-202 °C (fromEtOH/THF); Rf 0.41 (DCM); (found: C, 46.70; H, 2.97; N, 14.73. C11H8ClN3O2S requires C,46.90; H, 2.86; N, 14.92%); λmax(DCM)/nm 295 (log ε 4.12), 321 (4.25), 334 inf (4.18), 413(3.69); vmax/cm-1 3258m (N-H), 1680s, 1632s, 1589m, 1547s, 1518m, 1487w, 1439m, 1431s,1356m, 1315w, 1312w, 1287m, 1260m, 1240m, 1177m, 1169m, 997m, 908s, 868m, 810m,795m; δH(300 MHz; DMSO-d6) 10.32 (1H, s, NH), 8.39 (1H, dd, J 1.8, 1.8, Ar H), 8.04 (1H,ddd, J 8.1, 2.2, 1.0, Ar H), 7.72 (1H, ddd, J 7.7, 1.3, 1.1, Ar H), 7.51 (1H, dd, J 8.0, 8.0, Ar H),2.58 (3H, s, CH3); δC(75 MHz; DMSO-d6) 197.5 (Cq), 157.1 (Cq), 150.2 (Cq), 141.4 (Cq), 138.4(Cq), 137.2 (Cq), 129.0 (CH), 125.1 (CH), 123.9 (CH), 120.2 (CH), 26.7 (CH3); m/z (MALDITOF)284 (MH++2, 39%), 282 (MH+, 100), 265 (37), 240 (66).

Reference： [1]Kalogirou, Andreas S.; East, Michael P.; Laitinen, Tuomo; Torrice, Chad D.; Maffuid, Kaitlyn A.; Drewry, David H.; Koutentis, Panayiotis A.; Johnson, Gary L.; Crona, Daniel J.; Asquith, Christopher R. M. [Molecules, 2021, vol. 26, # 19]

88
[ 80-63-7 ]
[ 99-03-6 ]
methyl 3-(3-acetylphenyl)-2-bromo-2-chloropropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 1-(3-aminophenyl)ethanone With hydrogen bromide; sodium nitrite In water at 0 - 5℃; Stage #2: methyl 2-chloroacrylate With copper(ll) bromide In water; acetone at 30 - 35℃; Inert atmosphere;	Methyl 3-Aryl-2-bromo-2-chloropropanoates 3; General Procedure General procedure: The corresponding aniline 1 (0.10 mol) was added to a 46% aqueousHBr solution (26.5 mL, 0.22 mol). The mixture was then cooled to -5 °Cand a saturated solution of sodium nitrite (7.6 g, 0.11 mol) in waterwas added dropwise at such a rate that the temperature did not exceed5 °C. The resulting cold solution of freshly prepared diazoniumsalt 2 was added dropwise under vigorous stirring to a mixture ofCuBr2 (0.100 g, 0.448 mmol) and methyl 2-chloroacrylate (10.1 mL,0.10 mol) in acetone (50 mL) at 30-35 °C. The rate of the addition wasadjusted so that nitrogen evolved at a rate of 2-3 bubbles per second(addition time around 0.5 h). The mixture was then stirred until nitrogenno longer evolved; water (200 mL) was added, the organic layerwas separated, and the aqueous layer was extracted with dichloromethane(3 × 15 mL). The combined extracts were dried over MgSO4,evaporated, and the residue was distilled under reduced pressure

Reference： [1]Ostapiuk, Yurii V.; Shehedyn, Maksym; Barabash, Oksana V.; Demydchuk, Bohdan; Batsyts, Sviatoslav; Herzberger, Colin; Schmidt, Andreas [Synthesis, 2021, vol. 54, # 3, p. 732 - 740]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	99-03-6	MDL No. :	MFCD00007796
Formula :	C₈H₉NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CKQHAYFOPRIUOM-UHFFFAOYSA-N
M.W :	135.16	Pubchem ID :	7417
Synonyms :	3'-Aminoacetophenone	Chemical Name :	1-(3-Aminophenyl)ethanone

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.04
TPSA :	43.09 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.54 cm/s

Log Po/w (iLOGP) :	1.25
Log Po/w (XLOGP3) :	0.83
Log Po/w (WLOGP) :	1.48
Log Po/w (MLOGP) :	1.12
Log Po/w (SILICOS-IT) :	1.44
Consensus Log Po/w :	1.22

[ CAS No. 99-03-6 ] {[proInfo.proName]}

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[ 99-03-6 ] Synthesis Path-Upstream 1~13

[ 99-03-6 ] Synthesis Path-Downstream 1~88

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[ 99-03-6 ]

Zaleplon Intermediates

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[ 99-03-6 ]

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.58
Solubility :	3.56 mg/ml ; 0.0264 mol/l
Class :	Very soluble
Log S (Ali) :	-1.32
Solubility :	6.51 mg/ml ; 0.0482 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.34
Solubility :	0.615 mg/ml ; 0.00455 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.0

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Yield	Reaction Conditions	Operation in experiment
88.3%	Stage #1: With sulfuric acid In water at 45 - 50℃; for 0.5 h; Stage #2: With water; urea; sodium nitrite In water at 0 - 5℃; for 0.5 h; Stage #3: With sulfuric acid In 5,5-dimethyl-1,3-cyclohexadiene; water at 90℃; for 2 h;	In the reactor,Add 590g of water,270g mass fraction of 98percent concentrated sulfuric acid,135 g (1 mol) of 3-aminoacetophenone prepared by S2 was added thereto at a controlled temperature of 45 to 50 ° C,Insulation stirring 0.5h,Control the temperature at 0 ~ 5 ,Dropping sodium nitrite solution (sodium nitrite 77g and 190g water preparation,The mass fraction is 28.8percentAll drops),After the addition is completed,Add 2.8g of urea,Insulation diazotization reaction 0.5h,After completion of the reaction was added to the reaction solution from xylene,Water and concentrated sulfuric acid mixture of hydrolyzate (380g of xylene, 80g of water and 16g concentrated sulfuric acid),Heated to 90 hydrolysis reaction,Nitrogen release,Reflux 2h,After the completion of the hydrolysis reaction was cooled to 10 ~ 15 ,Insulation stirring 0.5h,filter,Washed,Dried to give pale yellow powder 3-hydroxyacetophenone 120g,The yield was 88.3percentThe tested melting point of 95-98 ;
80%	Stage #1: With sodium nitrite In water at 20℃; Milling; Green chemistry Stage #2: at 80℃; for 0.5 h; Neutral conditions; Green chemistry	General procedure: Aniline (1mmol, 0.095mL), silica sulfuric acid (0.75g) and sodium nitrite (1.7mmol, 0.12g) were ground in a mortar with a pestle for a few minutes to obtain a homogeneous mixture. Then, four drops of water were gradually added and the mixture was ground for 10min to give phenyl diazonium silica sulfate. Five drops of water were added to phenyl diazonium silica sulfate (1mmol) and the resulting mixture was simply blended and then placed into a covered petri dish. Then, the petri dish was placed in an oven at 60°C for 15min. After that, the reaction mixture was diluted with EtOAc (15mL) and filtered after vigorous stirring. The residue was extracted with EtOAc (2×10mL) and the combined organic layer was dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to afford the crude product. Further purification was performed by flash column chromatography and the pure phenol was obtained in 81percent (0.076g).

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: With sodium tetrahydroborate In ethanol at 0℃; for 3 h; Stage #2: With hydrogenchloride In ethanol; water	<Example 38> Synthesis of 8-[1-(Dimethylamino)ethyl]-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-5(6H)-one dihydrochloride Step 1: Synthesis of 1-(3-aminophenyl)ethanol [Show Image] 3-aminoacetophenon (2.0 g, 14.80 mmol) was dissolved in ethanol (25 ml) and added with sodium borohydride (1.4 g, 36.99 mmol) at 0 °C. The resulting mixture was stirred for 3 hours and poured into ice water. The mixture was neutralized with 2 N hydrochloric acid acqueous solution and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (1.7 g, yield:84percent, white solid). ¹H NMR(400MHz, CDCl₃); δ 7.13(t, J=8.0Hz, 1H), 6.76-6.72(m, 2H), 6.60(dd, J=8.0Hz, 2.4Hz, 1H), 4.81(m, 1H), 1.46(d, J=6.8Hz, 3H)
84%	Stage #1: With sodium tetrahydroborate In ethanol at 0℃; for 3 h; Stage #2: With water In ethanol	Step 1: Synthesis of 1-(3-aminophenyl)ethanol 3-aminoacetophenon (2.0 g, 14.80 mmol) was dissolved in ethanol (25 ml) and added with sodium borohydride (1.4 g, 36.99 mmol) at 0° C. The resulting mixture was stirred for 3 hours and poured into ice water. The mixture was neutralized with 2 N hydrochloric acid aqueous solution and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (1.7 g, yield:84percent, white solid). ¹H NMR(400 MHz, CDCl₃); δ 7.13(t, J=8.0 Hz, 1H), 6.76-6.72(m, 2H), 6.60(dd, J=8.0 Hz, 2.4 Hz, 1H), 4.81(m, 1H), 1.46(d, J=6.8 Hz, 3H)
76%	With [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; sodium formate In water at 30℃; for 24 h; Inert atmosphere; Schlenk technique	General procedure: In a schlenk tube, the chiral ligand (0.05 mmol) and the metallicprecursor (0.025 mmol) are dissolved in the water (4 mL). After 1 hof stirring at 30 °C, the sodium formate (10 mmol) and the ketone (1 mmol) were added to the aqueous solution. The biphasic solution was stirred at 30 for the indicated time and follow by TLC untilthe total reduction of ketone. The formed alcohol was separated from the catalyst by simple extraction with pentane (2 8 mL) and the organic layer was dried over MgSO4 and concentrated in vacuo.The crude residue was distilled in order to purify the alcohol.

Precautionary Statements-General
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P102	Keep out of reach of children.
P103	Read label before use
Prevention
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Response
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P320
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P321
P322
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P378
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P370 + P378	In case of fire:
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Storage
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P401
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P411
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P413
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