Name: 15690-24-1|(E)-3-(Furan-2-yl)acrylic acid|95%
Brand: Ambeed
SKU: A471566
Price: 9.0 USD
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1
[ 98-01-1 ]
[ 141-82-2 ]
[ 539-47-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: furfural; malonic acid With piperidine; pyridine at 20 - 100℃; for 3h; Stage #2: With hydrogenchloride In water	1 Reference Example 1 (2E)-3-(2-furyl)acrylic acid; [Show Image] To a mixture of 2-furfural (500 g, 5.20 mol) and malonic acid (595 g, 5.72 mol) in pyridine (500 mL) was added piperidine (50 mL, 0.505 mol) at room temperature, and the mixture was stirred at 100°C for 3 hr. The reaction solution was poured into water (1 L) and acidified with 6M hydrochloric acid. The resulting precipitate was collected by filtration to give the title compound (660 g, yield 92s). 1H-NMR (DMSO-d6) δ: (1H, d, J = 15.9 Hz) , 6.62 (1H, dd, J = 3.6, 1.6 Hz), 6.92 (1H, d, J = 3.6 Hz), 7.39 (1H, d, J = 15.9 Hz), 7.83 (1H, d, J = 1.6 Hz), 12.38 (1H, s).
90%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; 3-amino propanoic acid In ethanol at 20℃; stereoselective reaction;
87%	Stage #1: malonic acid In pyridine Stage #2: furfural In pyridine at 0 - 20℃; for 3h; Heating / reflux;

84%	With piperidine; pyridine at 110℃;	4.2 Synthesis of substituted acrylic acids (1a-1d) General procedure: Aromatic aldehyde (1mol), malonic acid (1.2mol) and piperidine (0.1mol) were dissolved in pyridine and refluxed at 110°C for 16-24h in oil bath. After the completion of reaction, the reaction mixtures were quenched by pouring it into cold dilute HCl solution. The crude product was adsorbed and loaded on the silica gel (100-200 mesh) column, and the compound was eluted with (20%) ethyl acetate in hexane to give pure compounds with 81-84% yield. 4.2.1.(E)-3-(furan-2-yl)acrylic acid (1a). Yield 84%; mp:147-149 °C; 1H NMR (400 MHZ, CDCl3) δ ppm: 11.43 (s, 1H), 7.56-7.53(m, 2H), 6.69 (d, J = 3.40 HZ, 1H), 6.51 (dd, JL = 3.40, JS = 1.80 HZ,1H), 6.34 (d, J = 15.68 HZ, 1H); 13C NMR (100 MHz, CDCl3) δ ppm:172.73, 150.65, 145.33, 133.08, 115.85, 114.90, 112.48; HRMS (ESI)m/z; calcd for C7H6NaO3+ ([M + Na]+) 161.0209, found 161.0214.
82%	In pyridine 1.) 100 deg C, 12 h, 2.) reflux;
78%	With aluminum potassium sulfate dodecahydrate for 0.05h; Microwave irradiation;
73.7%	With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 110℃; for 2h;	4.3 General synthetic procedure for compound (3-8) General procedure: The trans cinnamic acid derivatives (3-8) were synthesized by utilizing substituted benzaldehydes (1.0g, 1.0eq) in 100.0ml round bottom flask containing 15.0ml dimethylformide and malanoic acid (1.1eq). Diaza bicyclooctane (DABCO 1.0eq) was added as a catalyst and the temperature was raised to 110.0°C and maintained for 2.0h. The reaction was monitored by thin layer chromatography. After the completion of the reaction the reaction mass was quenched into cold water 40.0ml and extracted with ethyl acetate 2×25ml. The organic layer was dried with anhydrous sodium sulfate and concentrated under high vacuum, the resulted solid was washed with hexane (5.0ml), suck dry for 15.0min and then dried under vacuum at 45°C for 5.0h to yield the solid compound.
73%	With piperidine; pyridine at 90℃; for 1h;
72.7%	With piperidine; pyridine at 100℃; for 16h;	19.1 Step 1 (E) -3- (Furan-2-yl) acrylic acid To a mixture of furan-2-carbaldehyde (30 g 312 mmol) and malonic acid (35.7 g 343 mmol) in pyridine (300 mL) was added piperidine (3.09 mL 31.2 mmol) at rt and the mixture was stirred at 100 for 16 h. The reaction solution was poured into water (200 mL) and acidified with 6M hydrochloric acid. The resulting precipitate was collected by filtration to give (E) -3- (furan-2-yl) acrylic acid (32 g 227 mmol 72.7 yield) 1HNMR(400 MHz CD3OD) δ 7.61 (d J 1.6 Hz 1H) 7.42 (d J 15.6 Hz 1H) 6.73 (d J 3.2 Hz 1H) 6.53 (dd J 2.0 3.6 Hz 1H) 6.22 (d J 15.6 Hz 1H) ES-LCMS m/z 139.1 (M+H)
71%	With piperidine; triethylamine In toluene Reflux;
67.2%	In pyridine at 120℃;
66%	With piperidine; pyridine Reflux;	1 General procedure: A mixture of aromatic aldehyde (2.16 mmol), malonic acid (0.45 g, 4.32 mmol),Piperidine (2.0 mL), pyridine (20 mL) was heated at reflux for 3-40 h.Cooling to room temperature, 25% K2C03 solution to the reaction solution, stirring heating, liquid separation, the water phase with dilute hydrochloric acid for acidification, filtration, drying available crude product, after recrystallization or column chromatography available pure.
55%	With piperidine; pyridine at 110℃; for 2h;	2.2a Synthesis of (E)-3-(furan-2-yl)acrylic acid (1) To a solution of malonic acid (33.67 mg, 0.15 mmol) in pyridine (3 mL) were added piperidine (44.2 mg, 0.52 mmol) and furan-2-carbaldehyde (500 mg, 5.20 mmol) and stirred at 110°C for 2 h. TLC showed completion of reaction (TLC system: 20% EtOAc in Hexane, Rf: 0.5). Then the reaction mixture was concentrated in vacuo, water (10 mL) was added and neutralized with 6N HCl. The precipitate obtained was filtered, washed with water (3 mL), dried under vacuum to obtain 3-(furan-2-yl)acrylic acid (1). Brown solid; Yield: 100mg, 55%; M.p. 78-82°C; IR (KBr): νmax/cm-1 3327 (-COOH stretching); 1H NMR (400 MHz, DMSO-d6) δ 12.3 (s, 1H, -OH), 7.81 (s, 1H, Ar-H), 7.37 (d, J =15.8Hz, 1H, -C=CH-), 6.91 (d, J = 3.2 Hz, 1H, Ar-H), 6.61 (dd, J = 1.4, 3.6 Hz, 1H, Ar-H), 6.15 (d, J = 15.8 Hz, 1H, -C=CH-); 13C NMR (100 MHz DMSO-d6) δ 167.3(C=O), 150.3, 145.6 (Ar-C), 130.8, 116.1 (-HC=CH-), 115.3, 112.6 (Ar-C); APCI-MS m/z: 137 [M-H]+.
50%	With morpholine; pyridine
	With rac-Ala-OH at 100℃;
	With glycine at 100℃;
	With pyridine
	With ammonia stable β-<α-furyl>-acrylic acid;
	With piperidine; pyridine Yield given;
	In pyridine for 2.5h; Heating;
	With quinoline
	With piperidine In pyridine at 100℃; for 5.33333h; Heating / reflux;	1.a Example 1: 4-AMINO-3-(4-((2-FLUORO-5-(TRIFLUOROMETHYL) AMINOCARBONYLAMINO)PHENYL)-7- (3-CHLOROPHENYL))-FURO[3,2-C]PYRIDINE (1A); a) 3-(FURAN-2-YL)-ACRYLIC acid (2) The mixture of 2-furfural (15 g, 0.15 mol), malonic acid (17. 9 g, 0.17 mol) and piperidine (1. 5 ml, 0.016 mol) in 80 ml of pyridine was stirred for 5 hours at 100°C and then refluxed for 20 min, which was cooled down to room temperature and poured into water (180 ML), and resultant mixture was acidified with concentrated HCI. The generated precipitate was collected by filtration and dried under the reduced pressure to give 3- (FURAN-2-YL)-ACRYLIC acid (16.8 g). 1H NMR (400MHz, DMSO-d6) ppm 12. 44 (brs, 1H), 7. 83 (d, J = 1.8 Hz, 1 H), 7.40 (d, J = 15.9 Hz, 1 H), 6.93 (d, J = 3.3 Hz, 1 H), 6.63 (dd, J = 1.8, 3.3 Hz, 1H), 6.17 (d, J=15. 7HZ, 1H)
82 mg	With 1-n-butyl-3-methylimidazolim bromide at 60℃; for 72h;
	Stage #1: furfural; malonic acid With piperidine; pyridine at 80 - 115℃; Stage #2: With hydrogenchloride In water at 20℃;	(1) General Procedure for the Synthesis of α,β-Unsaturated Acid1 General procedure: To a solution of malonic acid (200 mmol) in pyridine (60 mL) was added aldehyde (150 mmol), the heterogeneous mixture was stirred at room temperature for several minutes. Piperidine (2.0 mL) was then added, and the mixture was heated to 80 °C slowly (about 30 min should be allowed for this period). After the reaction mixture was refluxed at 80 deg;C for 4-5 h, it was finally heated under reflux (110-115 °C) for additional 8 h. The reaction mixture was allowed to cool to room temperature, and then it was acidified by slowly pouring into hydrochloric acid (1.5 N, 90 mL) with stirring. The solid was separated by suction filtration and washed with cold water (3 times). The solid was then dried at 60 °C. It could be purified by recrystallization from methyl ethyl ketone (12 mL/1 g). The hot solution was then filtered rapidly through a steam-heated Büchner funnel and chilled for several hours. The pure product could be obtained after filtration and drying.
	With piperidine; pyridine for 1h; Reflux;
	With pyridine Heating;
	With piperidine In dimethyl sulfoxide at 100℃; for 12h; Schlenk technique;
	With pyridine for 12h; Reflux;
	With piperidine; pyridine In toluene for 12h; Reflux;
	With piperidine; pyridine for 12h; Reflux; Inert atmosphere;
	With [Hf₆O₄(OH)₄(2,2’-diamino-[1,1’-biphenyl]-4,4’-dicarboxylic acid)₆]10H₂O5DMF In N,N-dimethyl-formamide; toluene at 80℃; for 24h; Schlenk technique;

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP2100895, 2009, A1 Location in patent: Page/Page column 43-44
[2]Location in patent: experimental part Zhu, Lingjian; Lei, Ning; Miao, Zhenyuan; Sheng, Chunquan; Zhuang, Chunlin; Yao, Jianzhong; Zhang, Wannian [Chinese Journal of Chemistry, 2012, vol. 30, # 1, p. 139 - 143]
[3]Current Patent Assignee: LYONDELLBASELL INDUSTRIES N.V. - EP1216999, 2002, A1 Location in patent: Page 5
[4]Kumar, Gautam; Goutami Godavari, Ambati; Tambat, Rushikesh; Kumar, Siva; Nandanwar, Hemraj; Elizabeth Sobhia; Jachak, Sanjay M. [Bioorganic Chemistry, 2020, vol. 104]
[5]New, James S.; Christopher, William L.; Yevich, Joseph P.; Butler, Rhett; Schlemmer, R. Francis; et al. [Journal of Medicinal Chemistry, 1989, vol. 32, # 6, p. 1147 - 1156]
[6]Location in patent: experimental part Suresh, Dhruva Kumar; Sandhu, Jagir S. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2011, vol. 50, # 10, p. 1479 - 1483]
[7]Gayam, Venkatareddy; Ravi, Subban [European Journal of Medicinal Chemistry, 2017, vol. 135, p. 382 - 391]
[8]Olawode, Emmanuel O.; Tandlich, Roman; Prinsloo, Earl; Isaacs, Michelle; Hoppe, Heinrich; Seldon, Ronnett; Warner, Digby F.; Steenkamp, Vanessa; Kaye, Perry T. [Arkivoc, 2016, vol. 2016, p. 284 - 296] Olawode, Emmanuel O.; Tandlich, Roman; Prinsloo, Earl; Isaacs, Michelle; Hoppe, Heinrich; Seldon, Ronnett; Warner, Digby F.; Steenkamp, Vanessa; Kaye, Perry T. [Arkivoc, 2016, vol. 2016, # 6, p. 284 - 296]
[9]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2016/37578, 2016, A1 Location in patent: Page/Page column 145; 146
[10]Destro, Dario; Bottinelli, Carlo; Ferrari, Ludovica; Albanese, Domenico C. M.; Bencivenni, Grazia; Gillick-Healy, Malachi W.; Kelly, Brian G.; Adamo, Mauro F. A. [Journal of Organic Chemistry, 2020, vol. 85, # 8, p. 5183 - 5192]
[11]Xie, Yuanchao; Huang, Bing; Yu, Kexiang; Shi, Fangyuan; Xu, Wenfang [Medicinal Chemistry Research, 2013, vol. 22, # 7, p. 3485 - 3496]
[12]Current Patent Assignee: NANKAI UNIVERSITY - CN103626652, 2016, B Location in patent: Paragraph 0022; 0023; 0024; 0025; 0026
[13]Swamy, Ponnapalli Veerabhadra; Kambhampati, Pullaiah China; Chandrasekhar, Kothapalli Bonnoth; Thirupathi, Gugulothu; Sujitha, Pombala; Kumar, Chityal Ganesh; Kumar, Veeramachaneni Ganesh [Journal of Chemical Sciences, 2016, vol. 128, # 6, p. 929 - 939]
[14]Gucma, Miroslaw; Golbiewski, W. Marek; Krawczyk, Maria [RSC Advances, 2015, vol. 5, # 17, p. 13112 - 13124]
[15]Dakin [Journal of Biological Chemistry, 1910, vol. 7, p. 54]
[16]Dakin [Journal of Biological Chemistry, 1910, vol. 7, p. 54]
[17]Rajagopalan; Raman [Organic Syntheses, 1945, vol. 25, p. 51] Dutt [Journal of the Indian Chemical Society, 1923, vol. 1, p. 301][Chemisches Zentralblatt, 1925, vol. 96, # II, p. 1852]
[18]Knoevenagel [Chemische Berichte, 1898, vol. 31, p. 2619][Chemisches Zentralblatt, 1898, vol. 69, # II, p. 695]
[19]Brown, Thomas H.; Blakemore, Robert C.; Blurton, Peter; Durant, Graham J.; Ganellin, C. Robin; et al. [European Journal of Medicinal Chemistry, 1989, vol. 24, p. 65 - 72]
[20]Sandström; Kwiatkowski; Chattopadhyaya [Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1985, vol. 39, # 4, p. 273 - 290]
[21]Dalal; Dutt [Journal of the Indian Chemical Society, 1932, vol. 9, p. 313][Chemisches Zentralblatt, 1932, vol. 103, # II, p. 3705]
[22]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2004/100947, 2004, A2 Location in patent: Page 19-20; 16
[23]Location in patent: scheme or table Sharma, Nandini; Sharma, Upendra K.; Kumar, Rajesh; Katoch, Nidhi; Kumar, Rakesh; Sinha, Arun K. [Advanced Synthesis and Catalysis, 2011, vol. 353, # 6, p. 871 - 878]
[24]Xia, Ziming; Lv, Xin; Wang, Wencun; Wang, Xiaoxia [Tetrahedron Letters, 2011, vol. 52, # 38, p. 4906 - 4910]
[25]Location in patent: experimental part Yang, Shaoxiang; Kang, Tieniu; Rui, Changhui; Yang, Xinling; Sun, Yufeng; Cui, Zining; Ling, Yun [Chinese Journal of Chemistry, 2011, vol. 29, # 11, p. 2394 - 2400]
[26]Han, Sheng Hua; Chen, Jian Xin; Liu, Hong Yan; Zhang, Hai Rong; Ma, Peng Fei [Asian Journal of Chemistry, 2015, vol. 27, # 4, p. 1299 - 1303]
[27]Zhou, Mingxin; Zhou, Yao; Song, Qiuling [Chemistry - A European Journal, 2015, vol. 21, # 30, p. 10654 - 10658]
[28]Yan, Mi; Ma, Xiaodong; Dong, Ruiqian; Li, Xin; Zhao, Can; Guo, Zhenzhen; Shen, Yan; Liu, Fang; Ma, Ruixin; Ma, Shutao [European Journal of Medicinal Chemistry, 2015, vol. 103, p. 506 - 515]
[29]Du, Fangyu; Zhou, Qifan; Fu, Xiaoxiao; Shi, Yajie; Chen, Yuanguang; Fang, Wuhong; Yang, Jingyu; Chen, Guoliang [RSC Advances, 2019, vol. 9, # 5, p. 2498 - 2508]
[30]Gong, Pei-Xue; Xu, Fangning; Cheng, Lu; Gong, Xu; Zhang, Jie; Gu, Wei-Jin; Han, Wei [Chemical Communications, 2021, vol. 57, # 48, p. 5905 - 5908]
[31]Das, Aniruddha; Anbu, Nagaraj; Gogoi, Chiranjib; Dhakshinamoorthy, Amarajothi; Biswas, Shyam [European Journal of Inorganic Chemistry, 2021, vol. 2021, # 33, p. 3396 - 3403]

2
[ 98-01-1 ]
[ 108-24-7 ]
[ 539-47-9 ]

Yield	Reaction Conditions	Operation in experiment
50%	With hydrogenchloride; potassium carbonate at 90℃; for 3h;	24.1 Step 1: (E)-3-(Furan-2-yl)acrylic acid Acetic anhydride (21.25 g, 208.33 mmol) and K2CO3 (57.46 g, 419.42 mmol) were added to furan-2-carbaldehyde (20 g, 208.33 mmol). The resulting solution was allowed to react, with stirring, for 3 h at 90° C. Adjustment of the pH to 3 was accomplished by the addition of HCl (10%). The resulting solution was extracted with EtOAc (3300 mL). The organics were combined and washed with water (3100 mL), dried over Na2SO4, and concentrated by evaporation under vacuum to give 18 g (50%) of (E)-3-(furan-2-yl)acrylic acid as a light yellow solid.
	in Gegenwart basischer Katalysatoren;

Reference： [1]Current Patent Assignee: KALYPSYS, INC. - US2008/139558, 2008, A1 Location in patent: Page/Page column 28
[2]Simek; Hanus [Chemicke Zvesti, 1959, vol. 13, p. 108,113][Chem.Abstr., 1959, p. 17 994] Arata et al. [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1956, vol. 76, p. 211][Chem.Abstr., 1956, p. 14698] Scipioni; Borsetto [Annali di Chimica, 1952, vol. 42, p. 185] Gilman et al. [Iowa State College Journal of Science, 1930, vol. 4, p. 355,358]

3
[ 539-47-9 ]
[ 1487-18-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With copper(I) oxide In various solvent(s) at 200℃; for 3h;
	at 270 - 320℃;
	With quinoline; copper(II) sulfate

	With Camellia sinensis at 25℃; for 120h;
	With propane at 350℃;

Reference： [1]Schmidt; Werner [Synthesis, 1986, vol. No. 12, # 12, p. 986 - 992]
[2]Moureu; Dufraisse; Johnson [Annales de Chimie (Cachan, France), 1927, vol. <10> 7, p. 23,25]
[3]Pfau et al. [Helvetica Chimica Acta, 1935, vol. 18, p. 935,945] Hachihama et al. [Kogyo Kagaku zasshi / Journal of the Society of Chemical Industry, 1942, vol. 45, p. 471,475][J.Soc.Chem.Ind.Japan Spl., 1942, vol. 45, p. 189] Breault; Dermer [Proceedings of the Oklahoma Academy of Science, 1948, vol. 28, p. 82] Galimberti [Bollettino Scientifico della Facolta di Chimica Industriale di Bologna, 1940, vol. 1, p. 351] Pummerer; Stieglitz [Chemische Berichte, 1942, vol. 75, p. 1072,1080]
[4]Takemoto, Masumi; Achiwa, Kazuo [Tetrahedron Letters, 1999, vol. 40, # 36, p. 6595 - 6598]
[5]Current Patent Assignee: PHILLIPS 66 - US2431216, 1943, A

4
[ 539-47-9 ]
[ 935-12-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogen In ethyl acetate
93%	With hydrogen In methanol at 60℃; for 12h;	67.67A Example 67A; 3 -(tetrahydrofuran-2-yl)propanoic acid; (E)-3-(Furan-2-yl)acrylic acid (10 g, 72.4 mmol) was treated with Pd/C (Ig) in MeOH (100 mL). The mixture was heated at 60 0C at 60 psi under H2 for 12 hrs. After filtering off the catalyst, the filtrate was concentrated to afford 9.8 g (93 %) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.42 - 1.56 (m, 1 H) 1.77 - 1.96 (m, 4 H) 1.93 - 2.07 (m, 1 H) 2.41 - 2.56 (m, 2 H) 3.71 - 3.79 (m, 1 H) 3.82 - 3.94 (m, 2 H); MS (DCI/NH4+) m/z 145 (M + H)+.
	With ethanol; platinum Hydrogenation;

	With acetic acid; platinum Hydrogenation;
	With sodium carbonate; palladium Hydrogenation;
	catalytic hydrogenation;
	With hydrogen In methanol at 60℃; for 12h;	67.67A Example 67; N-r(5Z)-2-tert-butyl-4-(tetrahvdrofuran-2-ylmethyl)isothiazol-5(2H)-ylidene]-5-chloro-2- methoxybenzamide; Example 67A; 3 -(tetrahydrofuran-2-yl)propanoic acid; (E)-3-(Furan-2-yl)acrylic acid (10 g, 72.4 mmol) was treated with Pd/C (Ig) in MeOH (100 rnL). The mixture was heated at 60 0C at 60 psi under H2 for 12 hrs. After filtering off the catalyst, the filtrate was concentrated to afford 9.8 g (93 %) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.42 - 1.56 (m, 1 H) 1.77 - 1.96 (m, 4 H) 1.93 - 2.07 (m, 1 H) 2.41 - 2.56 (m, 2 H) 3.71 - 3.79 (m, 1 H) 3.82 - 3.94 (m, 2 H); MS (DCI/NH4+) m/z 145 (M + H)+.

Reference： [1]Grayson, David H.; McCarthy, Una; Roycroft, Edwin D. [Organic and Biomolecular Chemistry, 2003, vol. 1, # 11, p. 1930 - 1937]
[2]Current Patent Assignee: ABBVIE INC - WO2008/130953, 2008, A2 Location in patent: Page/Page column 79
[3]Kaufmann; Adams [Journal of the American Chemical Society, 1923, vol. 45, p. 3041]
[4]Kariyone [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1925, # 515, p. 1][Chemisches Zentralblatt, 1925, vol. 96, # I, p. 2377]
[5]Windaus; Dalmer [Chemische Berichte, 1920, vol. 53, p. 2307]
[6]Grayson, David H.; Roycroft, Edwin D. [Journal of the Chemical Society. Chemical communications, 1992, # 18, p. 1296 - 1297]
[7]Current Patent Assignee: ABBOTT LABORATORIES INC - WO2010/54024, 2010, A2 Location in patent: Page/Page column 94-95

5
[ 539-47-9 ]
[ 935-13-7 ]

Yield	Reaction Conditions	Operation in experiment
41%	With hydrogen; acetic acid;palladium on activated charcoal; at 20℃;	Step 2: 3-(Furan-2-yl)propanoic acid Pd/C (2 g, 0.96 mmol) was added to a solution of (E)-3-(furan-2-yl)acrylic acid (17 g, 110.87 mmol) in HOAc (200 mL) under nitrogen. Then nitrogen protection was removed and hydrogen atmosphere was introduced into the reaction mixture. The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 20 C. A filtration was performed and the filtrate concentrated by evaporation. The residue was dissolved in 300 mL of EtOAC, washed with water (2*50 mL), dried over Na2SO4, and concentrated by evaporation to afford 8 g (41%) of 3-(furan-2-yl)propanoic acid as a white solid. 1H NMR (400 MHz, CDCl3) delta 7.31 (d, 1H), 6.33 (d, 1H), 6.04 (d, 1H), 2.98 (d, 2H), 2.74 (m, 2H). LCMS: 139.0 (M+H)+.

Reference： [1]Organic and Biomolecular Chemistry,2004,vol. 2,p. 3434 - 3441
[2]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812
[3]Tetrahedron,1999,vol. 55,p. 11365 - 11384
[4]Chemical Communications,2005,p. 936 - 938
[5]Angewandte Chemie - International Edition,2014,vol. 53,p. 7785 - 7788
    Angew. Chem.,2014,vol. 53,p. 7919 - 7922,4
[6]Journal of Chemical Research, Miniprint,1983,p. 2201 - 2218
[7]Chemical Communications,2001,p. 2448 - 2449
[8]Journal of the Chemical Society. Perkin transactions II,1993,p. 1941 - 1946
[9]Patent: US2008/139558,2008,A1 .Location in patent: Page/Page column 28
[10]Chemische Berichte,1877,vol. 10,p. 356
[11]Tetrahedron Letters,1990,vol. 31,p. 5981 - 5984
[12]Journal of the Chemical Society,1959,p. 2767
[13]Journal of the Chemical Society,1953,p. 618,619
[14]Kogyo Kagaku zasshi / Journal of the Society of Chemical Industry,1954,vol. 57,p. 149,150
    Chem.Abstr.,1955,p. 1484
[15]Acta Chemica Scandinavica,1989,vol. 43,p. 381 - 385
[16]Justus Liebigs Annalen der Chemie,1932,vol. 497,p. 193,195
    Archiv der Pharmazie (Weinheim, Germany),1933,vol. 271,p. 431,434, 437

6
[ 64-17-5 ]
[ 539-47-9 ]
[ 53282-12-5 ]

Yield	Reaction Conditions	Operation in experiment
49%	With sulfuric acid for 16h; Reflux;	2.2b Synthesis of ethyl 3-(furan-2-yl)acrylate (2) To a solution of (E)-3 -(furan-2-yl)acrylic acid (1) (500mg, 3.60 mmol), in ethanol (5 mL) was added conc. H2SO4 (catalytic). The mixture was heated to reflux and maintained for 16 h. TLC showed completion of starting material (TLC system: 10% EtOAc in Hexane, Rf:0.5). The reaction mixture was cooled to room temperature and concentrated to obtain a residue. The residue was diluted with EtOAc (20 mL), washed with NaHCO3 solution (10 mL), water (10 mL), dried over anhydrous sodium sulphate, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain ethyl 3-(furan-2-yl)acrylate (2). Colorless liquid; Yield: 100 mg, 49%; IR (neat): νmax/cm-1 1709 (C=O stretching); 1H NMR (400 MHz, DMSO-d6) δ 7.82 (s, 1H, Ar-H), 7.44 (d, J = 15.8 Hz, 1H, -C=CH-), 6.95 (d, J = 3.3 Hz, 1H,Ar-H), 6.61 (dd, J = 1.7, 3.2 Hz, 1H, Ar-H), 6.25 (d,J = 15.8 Hz, 1H, -C=CH-), 4.15 (q, J = 7.0 Hz, 2H,-OCH2), 1.23 (t, J =7.0 Hz, 3H, -CH3); 13C NMR (100 MHz, DMSO-d6) δ 165.9 (C=O), 150.1, 145.8 (Ar-C), 115.8 (-HC=CH-), 114.7, 112.6 (Ar-C), 59.9 (-CH2),14 (-CH3); GC-MS m/z: 166.1 (M+).
	With hydrogenchloride
	With acetyl chloride

With sulfuric acid for 3h; Reflux;

Reference： [1]Swamy, Ponnapalli Veerabhadra; Kambhampati, Pullaiah China; Chandrasekhar, Kothapalli Bonnoth; Thirupathi, Gugulothu; Sujitha, Pombala; Kumar, Chityal Ganesh; Kumar, Veeramachaneni Ganesh [Journal of Chemical Sciences, 2016, vol. 128, # 6, p. 929 - 939]
[2]Current Patent Assignee: ALBERT AG CHEM WERKE - DE851064, 1945, C
[3]Current Patent Assignee: ALBERT AG CHEM WERKE - DE854525, 1952, C
[4]Xu, Yi; Chen, Lu; Yang, Yu-Wen; Zhang, Zhiqiang; Yang, Weibo [Organic Letters, 2019, vol. 21, # 17, p. 6674 - 6678]

7
[ 539-47-9 ]
[ 67998-15-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With pyridine; di-<i>tert</i>-butyl dicarbonate In ethyl acetate at 15 - 25℃; for 7h;
70%	With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In 1,4-dioxane at 25℃; for 15h;	General procedure for the synthesis of anhydride derivatives General procedure: To a round-bottom flask, cinnamic acid substrates (3.0 mmol) and CDMT (3.0 mmol) in dioxane (10 mL) were added, followed by that, NMM (3.0 mmol) was added to the reaction mixture. The resulted solution was stirred at room temperature for 15 h. The resulting mixture was cooled and then filtered using a syringe filter. Then the mass concentrated and further diluted with diethyl ether. The organic layer was washed with 5% citric acid and followed by 5% sodium bicarbonate. The organic layer was dried over sodium sulfate. The solvent was removed under reduced pressure, and the resulting crude product was purified by simple column chromatography (eluant hexane/ethyl acetate).
	With acetic anhydride at 110℃;

Reference： [1]Pozdnev, V. F. [Journal of general chemistry of the USSR, 1986, vol. 56, p. 613 - 617][Zhurnal Obshchei Khimii, 1986, vol. 56, # 3, p. 690 - 695]
[2]Raja, Gabriel Charles Edwin; Son, Yujeong; Kim, Myungjin; Lee, Sunwoo; Oh, Jonghoon [Synthetic Communications, 2017, vol. 47, # 24, p. 2449 - 2455]
[3]Ikeda [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1955, vol. 75, p. 60][Chem.Abstr., 1956, p. 929]

8
[ 53282-12-5 ]
[ 539-47-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium hydroxide for 4h; Heating;
	With sodium hydroxide; water
	With potassium hydroxide In ethanol at 20℃; for 2h;

	With sodium hydroxide In methanol; water at 20℃; for 5h;	General procedure for (E)-heteroarylacrylic acid 1 General procedure: To a solution of (E)-acrylate 9 (8.9 mmol) in MeOH (10 mL) was added 20% aqueous NaOH solution (5 mL), and then was stirred at rt for 5 h. The reaction mixture was diluted with water, and then was acidified with 10% HCl aqueous solution to precipitate the carboxylic acid. The precipitate was filtrated off to give the crude acrylic acid 1. (E)-3-(2-Furyl)acrylic acid 1a R (ATR) ν: 1681, 3073 cm-1. mp 139-140 °C (MeOH). 1H-NMR (300 MHz, CDCl3) δ: 6.33 (1H, d, J = 15.7 Hz), 6.49 (1H, dd, J = 1.8, 3.6 Hz), 6.67 (1H, d, J = 3.6 Hz), 7.51 (1H, d, J = 15.7 Hz), 7.52 (1H, d, J = 1.8 Hz); 13C-NMR (75 MHz, CDCl3) δ: 112.4, 114.8, 115.8, 133.0, 145.3, 150.6, 172.4. MS (EI) m/z: 138 (M+); HRMS (EI) Calcd for C7H6O3: 138.0317. Found: 138.0324.
330 mg	With lithium hydroxide monohydrate In tetrahydrofuran; water at 0 - 20℃;	S41.2 [0393] Step 2: Synthesis of ()-3-(furan-2-yl)acrylic acid . To the stirred solution of (E)-3-(furan-2-yl)acrylate (380 mg, 2.29 mmol, 1.0 equiv) in THF:Water (1 : 1) (10 ml) at 0 °C was added LiOH.H20 (288 mg, 6.87 mmol, 3.0 equiv.). The resulting reaction mixture was stirred overnight at room temperature. The progress of reaction was monitored through TLC. After completion of the reaction, the reaction mixture neutralized with 10% HC1, extracted with DCM (2x50 mL). The organic layers were combined, dried over anhydrous Na2S04 and evaporated to obtain crude residue which was purified by flash colum chromatography using DCM/MeOH as eluent to obtain as (E)-3-(furan-2-yl)acrylic acid as white soild (330 mg). LCMS: 139 [M+H]+.

Reference： [1]Paizs, Csaba; Katona, Adrian; Retey, Janos [Chemistry - A European Journal, 2006, vol. 12, # 10, p. 2739 - 2744]
[2]Posner; Sichert-Modrow [Chemische Berichte, 1930, vol. 63, p. 3078,3087]
[3]Basavaiah, Deevi; Jaganmohan Rao, Anumolu [Synthetic Communications, 2002, vol. 32, # 2, p. 195 - 201]
[4]Nishiyama, Takashi; Hatae, Noriyuki; Hayashi, Kaori; Obata, Manami; Taninaka, Kimiko; Yamane, Masahiro; Oda, Shota; Abe, Takumi; Ishikura, Minoru; Hibino, Satoshi; Choshi, Tominari [Heterocycles, 2017, vol. 95, # 1, p. 251 - 267]
[5]Current Patent Assignee: PRAXIS BIOTECH LLC - WO2019/195810, 2019, A2 Location in patent: Paragraph 0393; 0392

9
[ 75-03-6 ]
[ 539-47-9 ]
[ 53282-12-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With IRA 904 In acetonitrile 2.) 25 deg C, 12 h;
95%	With N-ethyl-N,N-diisopropylamine In acetonitrile at 60℃; for 18h;	401.401A Example 401; (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; Example 401A; Ethyl 2-Furylacrylate Ethyl iodide (64 ML, 0.796 mol) was added to furylacrylic acid (100 g, 0.724 mol), diisopropylethyl amine (140 ML, 0.796 mmol), in acetonitrile (1100 ML), and the mixture was heated to 60° C. After 18 h, the dark solution was cooled to room temperature and concentrated in vacuo.The resulting brown sludge was diluted with Et2O (500 ML), washed with 1 N aqueous HCl (2250 ML), washed with 0.2 N aqueous NaOH (2250 ML), washed with saturated aqueous NaH.CO3 (1*250 ML), dried (MgSO4), filtered, and concentrated to a black oil (114 g, 95%).1H NMR (DMSO-d6, 300 MHz) δ 7.84 (d, J=1.7 Hz, 1H), 7.46 (d, J=15.6 Hz, 1H), 6.97 (d, J=3.4 Hz, 1H), 6.33 (dd, J=3.4 Hz, J=1.7 Hz, 1H), 6.22 (d, J=15.9 Hz, 1H), 4.17 (q, J=7.1 Hz, 2H), 1.24 (t, J=7.1 Hz, 3H); MS (APCI) m/z 167 (M+H)+.

Reference： [1]Le Bigot, Yves; Delmas, Michel; Gorrichon, Jean-Pierre; Gaset, Antoine [Synthetic Communications, 1982, vol. 12, # 4, p. 327 - 332]
[2]Current Patent Assignee: ABBVIE INC - US2004/116518, 2004, A1 Location in patent: Page 29; 99

10
[ 539-47-9 ]
(E)-3-(2-furyl)acryloyl chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃;
95%	With thionyl chloride for 4h; Inert atmosphere; Reflux;	1.1 (1) Synthesis of trans-3-(2-furyl)acryloyl chloride (a-1) Add trans-3-(2-furyl)acrylic acid (0.003mol, 0.41g), 7mL of thionyl chloride, and reflux for 4h under nitrogen protection in a 50mL three-necked flask equipped with a thermometer and electromagnetic stirring.The remaining solvent was evaporated under reduced pressure, and the solvent was removed under reduced pressure to obtain 0.44 g of light yellow oil with a yield of 95.0%.
94%	With oxalyl dichloride at 60℃; for 2h; Inert atmosphere;

	With thionyl chloride; N,N-dimethyl-formamide In benzene
	With oxalyl dichloride In toluene at 80℃;
	With thionyl chloride for 2h; Ambient temperature;
	With thionyl chloride for 24h;
	With thionyl chloride In chloroform for 2h; Heating;
	With thionyl chloride In benzene for 4h; Heating;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0℃; for 1h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h;
	With thionyl chloride
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h;
	With oxalyl dichloride; N,N-dimethyl-formamide at 0℃;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0℃; for 1h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1.5h;
	With thionyl chloride In dichloromethane at 0 - 20℃;	1 Example 1 3-Furan-2-yl-1-morpholin-4-yl-propenone; [0227] Furylacrylic acid (25 g, 181 mmol) was added to 200 mL of methylene chloride and the reaction was cooled to 0°C. Thionyl chloride (19.8 mL, 272 mmol) was then added over 15 minutes. The solution was allowed to warm to room temperature overnight and the reaction went from cloudy to clear the next morning. In a separate flask 150 mL of methylene chloride and morpholine (47.5 mL, 545 mmol) were added and the flask was brought to 0°C. The solution containing the furan was then added dropwise by addition funnel to the cooled solution containing the morpholine. After addition the solution was allowed to warm to room temperature and stir for 1.5 hr. The reaction was then extracted twice with 1 N HCI, twice with brine, and dried over sodium sulfate. The organic layer was then decolorized by carbon and concentrated to dryness. This yielded a pale yellow solid (87% 32.5g, 156 mmol). ¹H NMR (CDCl3, 300 MHz) 8 3.60-3.78 (m, 8H), 6.48 (q, J=2 Hz, 1 H), 6.58 (d, J=3 Hz, 1 H), 6.78 (d, J=16 Hz, 1 H), 7.45-7.53 (m, 2H) ; MS (ESI (+)) m/z 208.1 (M+H+).
	With thionyl chloride In dichloromethane at 0 - 20℃;	1 Example 1 3-Furan-2-yl-1-morpholin-4-yl-propenone; [0227] Furylacrylic acid (25 g, 181 mmol) was added to 200 mL of methylene chloride and the reaction was cooled to 0°C. Thionyl chloride (19.8 mL, 272 mmol) was then added over 15 minutes. The solution was allowed to warm to room temperature overnight and the reaction went from cloudy to clear the next morning. In a separate flask 150 mL of methylene chloride and morpholine (47.5 mL, 545 mmol) were added and the flask was brought to 0°C. The solution containing the furan was then added dropwise by addition funnel to the cooled solution containing the morpholine. After addition the solution was allowed to warm to room temperature and stir for 1.5 hr. The reaction was then extracted twice with 1 N HCI, twice with brine, and dried over sodium sulfate. The organic layer was then decolorized by carbon and concentrated to dryness. This yielded a pale yellow solid (87% 32.5g, 156 mmol). ¹H NMR (CDCl3, 300 MHz) 8 3.60-3.78 (m, 8H), 6.48 (q, J=2 Hz, 1 H), 6.58 (d, J=3 Hz, 1 H), 6.78 (d, J=16 Hz, 1 H), 7.45-7.53 (m, 2H) ; MS (ESI (+)) m/z 208.1 (M+H+).
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Inert atmosphere;
	With thionyl chloride for 8h; Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran Cooling with ice;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 2h; Reflux; Inert atmosphere;
	With thionyl chloride; N,N-dimethyl-formamide In 1,2-dichloro-ethane for 4h; Reflux;	General procedure for the synthesis of (3E,5E)-1-((E)-3-arylacryloyl)-3,5-bis(pyridin-4-ylmethylene)piperidin-4-ones (8-17) General procedure: The mixture of appropriate substituted trans-cinnamic acid(3 mmol), thionyl chloride (6 mmol) and DMF (1 drop) in dry 1,2-dichloroethane (10 ml) were refluxed for 4 h under anhydrous conditions. Volatiles were then removed under reduced pressure at 50 °C. The residue (acid chloride) was dissolved in 1,2-dichloroethane (5 ml). This solution was added dropwise to an ice-cold stirred solution of 6 (2 mmol) and triethylamine (9 mmol) in 1,2-dichloroethane (20 ml) over 10 min under anhydrous conditions. The reaction mixture was stirred for an additional 17 h at room temperature. Upon completion of the reaction (monitored byTLC, solvent system 10% MeOH in DCM), the reaction mixture was washed successively with a saturated NaHCO3 solution (50 ml) and water (2 50 ml). The organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was rotary-evaporated to dryness to yield the crude product which was column-chromatographed on silica gel (eluent 2% MeOH in DCM) to obtain the pure product.
	With thionyl chloride; N,N-dimethyl-formamide In 1,2-dichloro-ethane for 4h; Reflux;	3.3 General procedure for the synthesis of (3E,5E)-1-((E)-3-arylacryloyl)-3,5-bis(pyridin-4-ylmethylene)piperidin-4-ones (8-17) General procedure: The mixture of appropriate substituted trans-cinnamic acid (3mmol), thionyl chloride (6mmol) and DMF (1 drop) in dry 1,2-dichloroethane (10ml) were refluxed for 4h under anhydrous conditions. Volatiles were then removed under reduced pressure at 50°C. The residue (acid chloride) was dissolved in 1,2-dichloroethane (5ml). This solution was added dropwise to an ice-cold stirred solution of 6 (2mmol) and triethylamine (9mmol) in 1,2-dichloroethane (20ml) over 10min under anhydrous conditions. The reaction mixture was stirred for an additional 17h at room temperature. Upon completion of the reaction (monitored by TLC, solvent system 10% MeOH in DCM), the reaction mixture was washed successively with a saturated NaHCO3 solution (50ml) and water (2×50ml). The organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was rotary-evaporated to dryness to yield the crude product which was column-chromatographed on silica gel (eluent 2% MeOH in DCM) to obtain the pure product.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 25 - 30℃; for 3h;	4.2 General procedure for the synthesis of title compounds 8 General procedure: To a methylene chloride (10mL) solution of substituted Carboxylic acid 3 (5mmol) in an ice bath was added oxalyl chloride (10mmol), and catalytic N,N-dimethylformamide, while the reaction contents were stirred continuously. The reaction mixture was allowed to stand at 25-30°C for 3h. Solvent distilled under reduced pressure and dried under high vacuum to remove oxalyl chloride. Reaction mass was dissolved in dichloromethane (10mL). The solution was added to the mixture of amine 7 (4.5mmol) and TEA (10mmol) and then allowed to stir at room temperature for overnight. Reaction mixture was washed with saturated sodium bicarbonate (20mL) and then with water (20mL). Organic solvent was dried over anhydrous Na2SO4, filtrated, and then evaporated to give solid. Crude solid product was recrystallized from suitable solvent to give title compounds 8a-e (Scheme 1) as solids.
	With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0℃; for 0.5h;	6.5. General methods for 11,12-cyclic carbonate azithromycin 4"-O-(trans-β-arylacrylamido)carbamoyl analogs (5-16) General procedure: General methods for 11,12-cyclic carbonate azithromycin 4"-O-(trans-β-arylacrylamido)carbamoyl analogs (5-16) To a solution of L1 (0.41 g, 2.74 mmol) in THF was added oxalyl chloride (1.03 g, 8.22 mmol) drop by drop and DMF (three drops) at 0 °C. The resulting solution was stirred for 0.5 h at the same temperature. Subsequently, the reaction was quenched in vacuum to remove THF and oxalyl chloride and afforded light-yellow residue. A solution of the key intermediate 4 (3 g, 3.43 mmol) and NaHCO3 (0.23 g, 2.74 mmol) in anhydrous THF was stirred at 0 °C. After addition of the above residue in THF drop by drop, the resulting solution was stirred for another 2 h at the same temperature. Then the reaction was concentrated in vacuum to remove THF and quenched with saturated NaHCO3. Subsequently, the aqueous layer was extracted with ethyl acetate (2 * 25 mL) and the combined organic layer was washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum to afford a crude product. A solution of the above crude product in methanol was heated to 55 °C and stirred for 12 h at the same temperature. Subsequent concentration of the reaction solution in vacuum provided the crude product of 5. The above crude product was purified by flash column chromatography eluting with 30:1 dichloromethane/methanol to afford the desired product 5. According to the above procedure, corresponding compounds 6-16 were prepared in yields ranging from 66% to 73%.
	With oxalyl dichloride; N,N-dimethyl-formamide Inert atmosphere; Reflux;	(E)-3-chloro-1-cinnamoyl-5,6-dihydropyridin-2(1H)-one (ZM90) General procedure: A solution of E-cinnamic acid (74 mg, 0.5 mmol) and oxalyl chloride (254 mg, 2 mmol) in dry THF was refluxed for 4 h under N2 atmosphere. The reaction was cooled to 0 °C and triethylamine (101 mg, 1 mmol) was dropwise added. The reaction solution was stirred for another 15 minutes at 0 °C. Then the lactam (66 mg, 0.5 mmol) in dry THF was slowly added and stirred at room temperature for overnight. The mixture was diluted with DCM (30 mL) and washed with saturated ammonium chloride solution (20 mL) and saturated saline solution (20 mL), dried over Na2SO4, concentrated and purified by column chromatography (Rf = 0.7, Ethyl Acetate/Petroleum Ether = 1:1) to afford ZM90, 100 mg, white solid, yield 76.9%.
	With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0℃; for 1.5h; Inert atmosphere;	General Method for Synthesis of Intermediate Acid Chlorides General procedure: To the acid (1 eq) in 1 mL of THF and 1 drop of DMF at 0°C, oxalyl chloride (1.2 eq) was added. The reaction was stirred under nitrogen for 1.5 hours and then the solution was concentrated. The acid chloride was continued to the next step.
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 5h; Inert atmosphere;
	With thionyl chloride In tetrahydrofuran for 2h; Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 25 - 30℃; for 3h;
	With thionyl chloride In dichloromethane Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 30℃;	4.9. General procedure for synthesis of intermediates 19a~c General procedure: Cinnamic acid 14a (1.05 g, 6.76 mmol) and oxalyl chloride(1.16 mL, 14.01 mmol), were dissolved in dry DCM (20 mL) at 0 °Cusing DMFas catalyst. Stirringwas kept for 2-3 h at 25-30° C. Afterthat time, the DCM was evaporated off under vacuum. The oil crudewas directly used in next step with no further purification. TheDCM (1 mL) solution of corresponding acyl chloride was added to the solution of methyl 3-amino-2-thiophenecarboxylate (1.06 g,6.75 mmol), TEA (0.94 mL, 6.8 mmol) in DCM (10 mL). Stirring waskept for 6-7 h at about 25 °C. After that time, the organic layer waswashed with saturated citric acid, water. At last, the organic layerwas dried by anhydrous Na2SO4.The DCM was evaporated to obtaincrude. The crude was purified by recrystallization using ethanol assolution to obtain title compound 15a.Compound 15a (1.00 g, 3.48 mmol) was dissolved in methanol(15 mL). 5 N NaOH solution (2 mL) was added to the mixture. Thenstirring was kept for 2-3 h at 60° C. While the reaction wasfinished, 2 N HCl solution was added until the value at pH 1. Andthen methanol was removed under reduced pressure. The precipitatewas filtered to give compound 16a.Compound 16a (1.00 g, 3.66 mmol) were dissolved in dry DCMand oxalyl chloride (0.62 mL, 7.32 mmol) was added slowly in icebath. Then DMF was added as catalyst. The mixture was warmed to25-30 °C and stirred for 3 h. After that time, the solution wasremoved and directly used without further purification. The crudewas dissolved in acetone (15 mL) and was slowly added NH3H2O(8 mL) in ice bath. After the operation, stirringwas kept for 3e4 h at25e30 C. While the reaction was finished, acetone was remove.The crude was added 2 N HCl solution until the value at pH 7. Theprecipitate was filtered to afford compound 17a.Compound 17a (1.00 g, 3.67 mmol) was suspended in methanoland cooled to 0° C. Sodium methoxide (30%, 5.5 mL) solution wasadded slowly drop-wise. And then, the mixture was refluxed for2-3 h. After that time, it was cooled to room temperature. Thesolvent was removed and acidified to pH 6-7 with 2 N HCl. Theprecipitate was produced and filtered, washed with water. Thecrude was recrystallized from acetone to obtain compound 18a.Compound 18a (1.11 g, 3.93 mmol) was added to phosphorusoxychloride (POCl3) (5 mL, 53.75 mmol) in ice bath. The suspensionwas heated and stirred at about 100 °C for 6-12 h under N2 atmosphere.After that time, the mixture was cooled to room temperatureand poured into ice/water (50 g). The suspension wasextracted with ethyl acetate (150 mL 3). The ethyl acetate layerwas washed with saturated NaHCO3, dried through anhydrousNa2SO4. Ethyl acetate was removed in vacuum to get intermediate19a. Compounds 19b ~ c were prepared according to the sameprocedure as compound 19a.
	With oxalyl dichloride In dichloromethane for 2h; Inert atmosphere;

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[32]Kerres, Sabine; Plut, Eva; Malcherek, Simon; Rehbein, Julia; Reiser, Oliver [Advanced Synthesis and Catalysis, 2019] Kerres, Sabine; Plut, Eva; Malcherek, Simon; Rehbein, Julia; Reiser, Oliver [Advanced Synthesis and Catalysis, 2019, vol. 361, # 6, p. 1400 - 1407]
[33]Shi, Jing Bo; Chen, Liu Zeng; Wang, Bao Shi; Huang, Xin; Jiao, Ming Ming; Liu, Ming Ming; Tang, Wen Jian; Liu, Xin Hua [Journal of Medicinal Chemistry, 2019, vol. 62, # 8, p. 4013 - 4031]
[34]Destro, Dario; Bottinelli, Carlo; Ferrari, Ludovica; Albanese, Domenico C. M.; Bencivenni, Grazia; Gillick-Healy, Malachi W.; Kelly, Brian G.; Adamo, Mauro F. A. [Journal of Organic Chemistry, 2020, vol. 85, # 8, p. 5183 - 5192]
[35]Chen, Liu Zeng; Shu, Hai Yang; Wu, Jing; Yu, Yun Long; Ma, Duo; Huang, Xin; Liu, Ming Ming; Liu, Xin Hua; Shi, Jing Bo [European Journal of Medicinal Chemistry, 2021, vol. 213]
[36]Kiledal, Sigrid A.; Jourdain, Roxane; Vellalath, Sreekumar; Romo, Daniel [Organic Letters, 2021, vol. 23, # 17, p. 6622 - 6627]

11
[ 539-47-9 ]
[ 138572-96-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With tetraethylammonium bromide; Dess-Martin periodane In dichloromethane at 20℃; for 0.25h;
88%	With diphosphorus tetraiodide; tetraethylammonium bromide In carbon disulfide at 20℃; for 8h;
57%	With ammonium cerium(IV) nitrate; lithium bromide In water; acetonitrile at 20℃; for 1h;

	With N-Bromosuccinimide; tetrabutylammonium trifluoroacetate In 1,2-dichloro-ethane Ambient temperature;
	With N-Bromosuccinimide; tetrabutylammonium trifluoroacetate In 1,2-dichloro-ethane at 20℃; for 27h;

Reference： [1]Telvekar, Vikas N.; Arote, Nitin D.; Herlekar, Omkar P. [Synlett, 2005, # 16, p. 2495 - 2497]
[2]Telvekar, Vikas N.; Chettiar, Somsundaram N. [Tetrahedron Letters, 2007, vol. 48, # 26, p. 4529 - 4532]
[3]Roy, Subhas Chandra; Guin, Chandrani; Maiti, Gourhari [Tetrahedron Letters, 2001, vol. 42, # 52, p. 9253 - 9255]
[4]Naskar, Dinabandhu; Chowdhury, Shantanu; Roy, Sujit [Tetrahedron Letters, 1998, vol. 39, # 7, p. 699 - 702]
[5]Naskar, Dinabandhu; Roy, Sujit [Tetrahedron, 2000, vol. 56, # 10, p. 1369 - 1377]

12
[ 95-14-7 ]
[ 539-47-9 ]
[ 519054-08-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In dichloromethane at 25℃; for 0.5h; Stage #2: 3-(fur-2-yl)crotonic acid In dichloromethane at 25℃; for 3h;
54%	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In dichloromethane at 20℃; for 0.5h; Stage #2: 3-(fur-2-yl)crotonic acid In dichloromethane at 20℃; for 3h;
	With thionyl chloride

	With thionyl chloride
	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In dichloromethane at 25℃; for 0.5h; Stage #2: 3-(fur-2-yl)crotonic acid In dichloromethane at 25℃; for 2h;	Method A (SOCl2/BtH Method): General procedure: To a solution of benzotriazole (BtH, 40 mmol) in CH2Cl2 (50 mL) was added SOCl2 (10 mmol), and the reaction mixture was stirred at 25 °C for 0.5 h. Then carboxylic acid (10 mmol) was added and the mixture was stirred for additional 2 h. The white precipitate was filtered off and washed with CH2Cl2 (2 x 50 mL). The combined organic phase was washed with aq. 2 N NaOH (3 x 60 mL), dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash chromatography on silica gel (EtOAc/Petrol = /6, v/v). 1

Reference： [1]Katritzky, Alan R.; Meher, Nabin K.; Singh, Sandeep K. [Journal of Organic Chemistry, 2005, vol. 70, # 19, p. 7792 - 7794]
[2]Aitken, R. Alan; Murray, Lorna [Journal of Organic Chemistry, 2008, vol. 73, # 24, p. 9781 - 9783]
[3]Katritzky, Alan R.; Widyan, Khalid; Kirichenko, Kostyantyn [Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5802 - 5804]
[4]Location in patent: body text Katritzky, Alan R.; Gyanda, Reena; Meher, Nabin K.; Song, Yuming [Heterocycles, 2009, vol. 77, # 2, p. 1249 - 1259]
[5]Xia, Ziming; Lv, Xin; Wang, Wencun; Wang, Xiaoxia [Tetrahedron Letters, 2011, vol. 52, # 38, p. 4906 - 4910]

13
[ 539-47-9 ]
2-[(E)-2-nitroethenyl]furan [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With ammonium cerium(IV) nitrate In acetonitrile at 20℃; for 1.5h;
41%	With tert.-butylnitrite; copper(l) chloride In acetonitrile at 80℃;
41%	With copper(II) nitrate In acetonitrile at 110℃; for 8h; Sealed tube; Green chemistry; regioselective reaction;	General procedure for synthesis of (E)-nitroolefins 3a-l General procedure: A 25-mL Schlenk tube was charged with α,β-unsaturated acid (0.4 mmol), Cu(NO3)2 (0.48 mmol), and CH3CN (2 mL). The tube was sealed, then the mixture was stirred under air at 110 °C for 8 h. After completion of the reaction as monitored by thin-layer chromatography (TLC), H2O (5 mL) was added. The mixture was extracted with dichloromethane (3 X 4 mL). The combined organic layers were washed with saturated sodium bicarbonate solution (10 mL) and water (10 mL), dried over anhydrous Na2SO4, then concentrated by rotary evaporator. Finally, the residue was purified by column chromatography on silica gel (mobile phase: petroleum ether/ethyl acetate 6:1) to provide the desired products (3). (E)-(2-Nitrovinyl)benzene (3a) [18, 19, 21]

Reference： [1]Sridhar Rao; Srinivas; Suresh Babu; Madhusudana Rao [Tetrahedron Letters, 2005, vol. 46, # 47, p. 8141 - 8143]
[2]Rokade, Balaji V.; Prabhu, Kandikere Ramaiah [Organic and Biomolecular Chemistry, 2013, vol. 11, # 39, p. 6713 - 6716]
[3]Luo, Zai-Gang; Xu, Feng; Fang, Yu-Yu; Liu, Peng; Xu, Xue-Mei; Feng, Cheng-Tao; Li, Zhong; He, Jie [Research on Chemical Intermediates, 2016, vol. 42, # 6, p. 6079 - 6087]

14
[ 539-47-9 ]
[ 25525-85-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 3-(fur-2-yl)crotonic acid With thionyl chloride In tetrahydrofuran at 50℃; for 1h; Stage #2: With ammonium hydroxide In tetrahydrofuran at 0℃; for 0.0833333h;
92%	Stage #1: 3-(fur-2-yl)crotonic acid With thionyl chloride In chloroform at 20℃; for 12h; Stage #2: With sodium hydroxide; ammonia In chloroform cooling; Further stages.;
	Multi-step reaction with 2 steps 1: phosphorus pentachloride 2: benzene; ammonia

With pyridine; di-<i>tert</i>-butyl dicarbonate; ammonium bicarbonate In tetrahydrofuran at 20℃; for 6h;

Reference： [1]Al-Huniti, Mohammed H.; Rivera-Chávez, José; Colón, Katsuya L.; Stanley, Jarrod L.; Burdette, Joanna E.; Pearce, Cedric J.; Oberlies, Nicholas H.; Croatt, Mitchell P. [Organic Letters, 2018, vol. 20, # 19, p. 6046 - 6050]
[2]Burgaz, E. Vildan; Yilmaz, Mehmet; Pekel, A. Tarik; Öktemer, Atilla [Tetrahedron, 2007, vol. 63, # 30, p. 7229 - 7239]
[3]Rinkes [Recueil des Travaux Chimiques des Pays-Bas, 1920, vol. 39, p. 205]
[4]Olawode, Emmanuel O.; Tandlich, Roman; Prinsloo, Earl; Isaacs, Michelle; Hoppe, Heinrich; Seldon, Ronnett; Warner, Digby F.; Steenkamp, Vanessa; Kaye, Perry T. [Arkivoc, 2016, vol. 2016, p. 284 - 296]

15
[ 539-47-9 ]
[ 119924-26-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	With diphenyl phosphoryl azide; triethylamine In tetrahydrofuran at 25℃; for 4h; Cooling with ice;	19.2 Step 2 (E)-3-(furan-2-yl)acryloyl azide To a mixture of (E) -3- (furan-2-yl) acrylic acid (25 g 181 mmol) and Et3N (30.3 mL 217 mmol) in THF (50 mL) was added DPPA (54.8 g 199 mmol) under ice-cooling. The mixture was stirred at 25 for 4 h. The reaction solution was poured into a mixture of EA (300 mL) and saturated aqueous NaHCO3solution (300 mL) and the mixture was extracted with EA (200 mL) . The extract was dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The residue was washed with MeOH to give (E) -3- (furan-2-yl) acryloyl azide (24 g 144 mmol 80 yield) 1HNMR(400 MHz CDCl3) δ 7.53-7.50 (m 1H) 7.47 (s 1H) 6.71 (d J 3.2 Hz 1H) 6.50 (dd J 2.0 3.6 Hz 1H) 6.30 (d J 3.6 Hz 1H)
74%	With diphenyl phosphoryl azide; triethylamine In tetrahydrofuran at 20℃; for 4h; Cooling with ice;	2 Reference Example 2 (2E)-3-(2-furyl)acryloyl azide; [Show Image] To a mixture of (2E)-3-(2-furyl)acrylic acid (660 g, 4.78 mol) and triethylamine (800 mL, 5.74 mol) in tetrahydrofuran (960 mL) was added diphenylphosphoryl azide (1.13 L, 5.26 mol) under ice-cooling. After stirring at room temperature for 4 hr, the reaction solution was poured into a mixture of ethyl acetate and saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was washed with methanol to give the title compound (580 g, yield 74%). 1H-NMR (DMSO-d6) δ: (1H, d, J = 15.7 Hz) , 6.67 (1H, dd, J = 3.4, 1.8 Hz), 7.10 (1H, d, J = 3.4 Hz), 7.56 (1H, d, J = 15.7 Hz), 7.88 - 7.94 (1H, m).
59%	With diphenyl phosphoryl azide; triethylamine In tetrahydrofuran at 20℃; for 4h;	221.221A (E)-3-(Furan-2-yl)acryloyl azide To a stirred solution of furyl acrylic acid (2.028 g, 14.68 mmol) in THF (40 mL) at 0 °C, was added triethylamine (2.6 mL, 18.65 mmol) and diphenylphosphorylazide (3.7 mL, 17.17 mmol) dropwise. The reaction was stirred at rt for 4 h, then the mixture was added to a mixture of ethyl acetate and sat. sodium bicarbonate. The aqueous phase was extracted with ethyl acetate (1 x) and the combined organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was triturated twice with methanol and filtered to give the title material (1.413g, 59%) as a beige solid. LC (Method A): 1.765 min. 1H NMR (DMSO-d6) δ ppm: 7.94 (s, 1H), 7.59 (d, J=15.6 Hz, 1H), 7.12 (d, J=3.6 Hz, 1H), 6.70 (m, 1H), 6.24 (d, J=15.6 Hz, 1H).

	Multi-step reaction with 2 steps 1: thionyl chloride 2: 75 percent / sodium azide / acetonitrile; H₂O / 16 h / 20 °C
	With diphenyl phosphoryl azide; triethylamine In tetrahydrofuran at 0 - 20℃; for 4h;	1.b b) 3-(FURAN-2-YL)-ACRYLOYL azide (3) To the solution of 3-(FURAN-2-YL)-ACRYLIC acid (15.7 g, 0.11 mol) and Et3N (19 ml, 0.14 mol) THF (300 ml) was added DPPA (27 ml, 0.13 MMOL) at 0°C and stirred for 4 hours at room temperature; the solution was poured into the mixture of ethyl acetate and saturated NAHCO3. The organic phase was separated, dried over NA2SO4 and then concentrated. During evaporation, precipitate was generated, which was collected and washed with MEOH, and dried under the reduced pressure to give 3- (FURAN-2-YL)-ACRYLOYL azide (12.6 g). 1H NMR (400MHZ, DMSO-D6) ppm 7.93 (d, J = 1.5 Hz, 1H), 7.59 (d, J = 15.7 Hz, 1H), 7.12 (d, J = 3.3 Hz, 1 H), 6.70 (dd, J = 1.9, 3.4 Hz, 1 H), 6.25 (d, J = 15.7 Hz, 1 H).
	With diphenyl phosphoryl azide; triethylamine In benzene at 80℃; for 3h;	1.1 1) Synthesis of HJH1412O6: (75)-(+)-2-(Furan-2-yl) vinylcarbamic acid, 8, 8-dimethyl-2-oxo-6,7-di- hydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester 10139] [Step 1] Trans-3-(2-thranyl)acrylic acid (500 mg,3.37 mmol) was dissolved in 20 mE of dry benzene in a round-bottom flask, and then, triethyamine (TEA, 234 jii, 1.683 mmol) and diphenyl phosphoryl azide (DPPA, 362 jii, 1 .683 mmol) were add thereto for a reaction at a temperature of 80° C. for 3 hours. After an extraction process using water and ethylacetate was performed on the mixed solution, a dehydration process using sodium sulfate was performed thereon, followed by being concentrated under reduced pressure.
	Stage #1: 3-(fur-2-yl)crotonic acid With chloroformic acid ethyl ester; triethylamine In acetone at 20℃; for 1h; Stage #2: With sodium azide In water; acetone at 0℃; for 1h;	3 0154] As shown above, furylacrylic acid (4,5. 0 g, 36. 23 mmol) is treated with ethyl chloroformate (4. 83 ml, 50. 72 mmol) in dry acetone (50 ml) in the presence of triethyl amine (6.05 ml, 43.5 mmol). After stirring at room temperature for 1 hour, sodium azide (3.53 g, 53035 mmol) in water (10 ml) is added at 0 °C and the suspension is stirred for 1 hour. The reaction mixture is diluted with icy water (150 ml) and extracted with benzene (70 ml X 3). The organic layer is dried with anhydrous sodium sulfate, filtered, and concentrated to a small volume (-60 ml).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2016/37578, 2016, A1 Location in patent: Page/Page column 146
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP2100895, 2009, A1 Location in patent: Page/Page column 44
[3]Current Patent Assignee: UNIVERSITY OF MONTREAL; BRISTOL-MYERS SQUIBB CO - WO2013/163244, 2013, A1 Location in patent: Paragraph 221A
[4]Katritzky, Alan R.; Widyan, Khalid; Kirichenko, Kostyantyn [Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5802 - 5804]
[5]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2004/100947, 2004, A2 Location in patent: Page 20; 16
[6]Current Patent Assignee: PUSAN NATIONAL UNIVERSITY - US2017/129904, 2017, A1 Location in patent: Paragraph 0138; 0139; 0146; 0159
[7]Current Patent Assignee: ASTRAZENECA PLC - WO2005/67900, 2005, A2 Location in patent: Page/Page column 39-40

16
1,4-diazabicyclo[3.2.2]nonane dihydrochloride [ No CAS ]
[ 539-47-9 ]
[ 660860-13-9 ]

Yield	Reaction Conditions	Operation in experiment
40%	With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 20h;	5 Example 5: (E)-1-(1,4-Diazabicyclo[3.2.2]non-4-yl)-3-(furan-2-yl)propenone (E)-3-Furan-2-yl-acrylic acid (69 mg, 0.50 [MMOL),] 1, [4-DIAZA-BICYCLO] [[3.] 2.2] nonane dihydrochloride (100 mg 0.50 mmol), 1-hydroxybenzotriazole hydrate (68 mg, 0. 50 [MMOL),] 0- (benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (161 mg, 0. 50 [IIIL,)] and diisopropylethylamine (0.35 mL, 250 mg, 2.0 mmol) in dry N,N-dimethylformamide (2 mL) were stirred at ambient [TEMPERATURE IBF] 20 h. The reaction mixture was poured into 1N sodium [HYDROXIDE] solution and extracted with ethyl acetate (2x). The [CTHYL] acetate layers were combined and washed with water [(2X). THE SOLVENT] was blown off with a stream of nitrogen to yield (E)-1-(1,4-diazabicyclo [3.2. 2]non-4-yl)-3-(furan-2-yl)propenone (49 mg, [40%) AS] a beige solid, MS (APCI+) 247 [M+1]+ 1(H-NMR (300 [MHZ,] CDCl3) : 5 [7.] [98-7.] 73 [(IFT, M),] 7. [42-7@ ]23 [(11. 1,] m), 6.97-6.76 (2H, m), 6.63-6. 53 [(IH,] [M),] 4. 56-4. 26 (1H, m), 3. 80-3.66 (2H, m), 3. 02-2, 77 [(611, NI), 1. 97-1.] 53 [(41-R,] m)

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2004/16616, 2004, A1 Location in patent: Page 10 - 11

17
[ 67-63-0 ]
[ 539-47-9 ]
[ 140138-10-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: 3-(fur-2-yl)crotonic acid With thionyl chloride In chloroform at 70℃; for 1h; Stage #2: isopropyl alcohol With pyridine In dichloromethane at 0 - 20℃;	4.1 Isopropyl (E)-3-furan-2-ylacrylate 1.46 ml of thionyl chloride (20 mmol) were added to a solution of 1.38 g of 3-(2-furyl)acrylic acid (10 mmol) in 10 ml of chloroform and 0.1 ml of DMF. The solution was warmed to 70° C. and kept at this temperature for 1 h, then the solvents were removed under reduced pressure and the residue was dissolved in 6.6 ml of DCM and 3.3 ml of pyridine and subsequently cooled to 0° C. 0.96 ml of 2-propanol (12.5 mmol) was added, the temperature was increased to RT and the reaction mixture was stirred for 2.5 h. It was acidified with 30 ml of 1 M hydrochloric acid and extracted with 150 ml of ethyl acetate. The organic phase was washed with aqueous sodium hydrogencarbonate solution, dried over sodium sulfate, filtered and the solvents were removed under reduced pressure. 1.72 g (yield: 96%) of the title compound were obtained. LC/MS (Method D) (M+H-isopropyl)+139

Reference： [1]Current Patent Assignee: SANOFI - US2009/233949, 2009, A1 Location in patent: Page/Page column 11

18
[ 477532-70-0 ]
[ 539-47-9 ]
[ 1359767-75-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 15h;	4.7.15. Methyl (S)-2-[(2E,4E)-5-methylhexadienoyl]-7-(2-{5-methyl-2-[(1E)-5-methylhexen-1-yl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (15a) General procedure: To a solution of 12i (700 mg, 1.70 mmol) in CH2Cl2 (7 ml) was added (2E,4E)-5-methylhexadienoic acid (180 mg, 2.22 mmol) and EDC (490 mg, 2.56 mmol) under ice-cooling, and the mixture was stirred at room temperature for 15 h. The reaction mixture was washed with water and saturated brine and dried over Na2SO4. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give 15a (700 mg, 79% yield) as an oil.

Reference： [1]Location in patent: experimental part Otake, Kazuya; Azukizawa, Satoru; Fukui, Masaki; Kunishiro, Kazuyoshi; Kamemoto, Hikaru; Kanda, Mamoru; Miike, Tomohiro; Kasai, Masayasu; Shirahase, Hiroaki [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 2, p. 1060 - 1075]

19
[ 3282-30-2 ]
[ 539-47-9 ]
C₁₂H₁₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at -78 - 0℃; for 1.5h; Inert atmosphere;
	With triethylamine In tetrahydrofuran at 0℃; for 0.75h;	4.7. General procedure for the synthesis of compounds 12-31 General procedure: (i) To a stirred solution of trimethoxy cinnamic acid (1 eq) in dry THF (3 mL) was added Et3N (1.5 eq) at 0 °C. To this reaction mixture pivaloyl chloride (1.1 eq) was added and allowed to stir for 45 min, reaction progress was monitored by TLC. After completion of the reaction, this mixture was used for the next step without purification. (ii) To a stirred solution of 9 (1.1 eq) in freshly distilled THF (2 mL), was added 1.1 eq of n-BuLi under inert atmosphere at -78 °C. After being stirred for 45 min, the mixed anhydride prepared from above procedure was added and the resultant reaction mixture was allowed to stir for 1 h. After completion of the reaction, mixture was quenched with saturated NH4Cl (1 mL) then extracted in to ethylacetate (5 mL). The organic layer was separated washed with sat. NaCl and dried over anhydrous Na2SO4. The combined organic layers were evaporated to dryness to give crude product which was purified by flash column chromatography on silica gel (60-120 mesh) using hexane/EtOAc (7:3) as eluent to give the desired products.
	With triethylamine In dichloromethane at 0℃; for 0.5h;	4.2.2. General procedures for the preparation of 6e29 General procedure: Firstly, the cinnamic acid analogues (1 equiv.) with differentsubstituents are added, dropwise stir in triethylamine ice bath for15 min then add trimethylacetyl chloride to protect the NeH at oneend. After concentration under reduced pressure, the residue wasquickly purified by using a silica gel column (PE/EtOAc). Here, donot contact water for reaction and products, and it needs to bequickly purified and concentrated. Concentrated 2-imidazolidone(1 equiv.) were added to absolute tetrahydrofuran or dichloromethaneunder nitrogen, and added NaH (3 equiv.) to the reactionmixturewas stirred at 0 C for 15 min. Then add the above productsto the reaction mixture was stirred at 0 C for 30 min. After thereaction was completed, used quenching with saturated NaHCO3solution, and then the mixed liquid was extracted twice with ethylacetate. The combined extracts were then washed with H2O andbrine and dried over anhydrous Na2SO4. After concentration underreduced pressure, the residue was quickly purified by using a silicagel column (PE/EtOAc).

Reference： [1]Location in patent: experimental part Nie, Lei; Yang, Rui; Zhang, Conghai; Yin, Haichuan; Yan, Shengjiao; Lin, Jun [Chinese Journal of Chemistry, 2012, vol. 30, # 2, p. 460 - 465]
[2]Rao, Vidadala Ramasubba; Muthenna, Puppala; Shankaraiah, Gundeti; Akileshwari, Chandrasekhar; Babu, Kothapalli Hari; Suresh, Ganji; Babu, Katragadda Suresh; Chandra Kumar, Rotte Sateesh; Prasad, Kothakonda Rajendra; Yadav, Potharaju Ashok; Petrash, J. Mark; Reddy, Geereddy Bhanuprakash; Rao, Janaswamy Madhusudana [European Journal of Medicinal Chemistry, 2012, vol. 57, p. 344 - 361]
[3]Ji, Limei; Qu, Lailiang; Wang, Cheng; Peng, Wan; Li, Shang; Yang, Huali; Luo, Heng; Yin, Fucheng; Lu, Dehua; Liu, Xingchen; Kong, Lingyi; Wang, Xiaobing [European Journal of Medicinal Chemistry, 2021, vol. 210]

20
[ 33513-42-7 ]
[ 539-47-9 ]
[ 111252-81-4 ]

Yield	Reaction Conditions	Operation in experiment
86%	With di-tert-butyl peroxide; copper(II) sulfate at 100℃; for 24h; Schlenk technique; Inert atmosphere;	15 General procedure for copper-catalyzed direct amidation between cinnamic acid and N-substituted formamide General procedure: CuSO4 (0.06 mmol) and cinnamic acid (0.3 mmol) were added to a Schlenk tube equipped with a magnetic stir bar under argon atmosphere. Then N-substituted formamide (2.0 mL) and DTBP (di-tert-butyl peroxide, 0.6 mmol) were added under Ar. The resulting reaction mixture was kept stirring until TLC monitoring indicated the complete disappearance of the starting material. At the end of the reaction, the reaction mixture was cooled to room temperature and was diluted with ethyl acetate and water was added. The combined organic phase was dried over anhydrous Na2SO4. After removal of the solvent, the residue was subjected to column chromatography on silica gel using ethyl acetate and petroleum ether mixtures to afford the corresponding product.
82%	With tert.-butylhydroperoxide; copper(II) oxide In water at 80℃; for 12h; regioselective reaction;

Reference： [1]Yan, Hong; Yang, Hailong; Lu, Linhua; Liu, Defu; Rong, Guangwei; Mao, Jincheng [Tetrahedron, 2013, vol. 69, # 35, p. 7258 - 7263]
[2]Priyadarshini; Amal Joseph; Lakshmi Kantam [RSC Advances, 2013, vol. 3, # 40, p. 18283 - 18287]

21
[ 123-91-1 ]
[ 539-47-9 ]
(E)-2-(2-(furan-2-yl)vinyl)-1,4-dioxane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With iron(III)-acetylacetonate; di-tert-butyl peroxide at 120℃; for 24h; Schlenk technique; Inert atmosphere; stereoselective reaction;	General procedure decarboxylative sp3(C)-sp2(C) coupling General procedure: To a Schlenk tube equipped with a magnetic stir bar were added Fe(acac)3 (21.2 mg, 0.06mmol) and cinnamic acid (0.3 mmol) under nitrogen. cyclic ether (2.0 mL) and DTBP(di-tert-butyl peroxide, 0.6 mmol, 113 μL) were added under nitrogen. The resulting reactionmixture was kept stirring at the 120 oC for 24 h. After required reaction time, the mixture wascooled down to room temperature. Evaporation of the solvent followed by purification by flashchromatography (petroleum ether/ethyl acetate) afforded the corresponding product 5 or 6.

Reference： [1]Zhao, Jincan; Zhou, Wei; Han, Jianlin; Li, Guigen; Pan, Yi [Tetrahedron Letters, 2013, vol. 54, # 48, p. 6507 - 6510]

22
tert-butyl (1R,5S)-7-(1H-imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-carboxylate [ No CAS ]
[ 539-47-9 ]
C₁₉H₂₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: tert-butyl (1R,5S)-7-(1H-imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-carboxylate With methyl iodide In tetrahydrofuran; acetonitrile at 20℃; for 24h; Stage #2: 3-(fur-2-yl)crotonic acid In acetonitrile at 20℃; for 24h;	4.10 General procedure C: synthesis of N-tboc protected bispidinecarboxamides General procedure: Methyl iodide (570 mg, 4 mmol) was added to a stirred solution of 12 (320 mg, 1 mmol) dissolved in dry MeCN (2 mL) and dry THF (2 mL) at rt. The volatiles were removed under reduced pressure after 24 h, the residue was dissolved in dry MeCN (4 mL), and Et3N (101 mg, 1 mmol) and the appropriate carboxylic acid (1 mmol) were added. The solution was allowed to stir at rt for 12-120 h before the volatiles were removed under reduced pressure. The residue was purified by flash chromatography (silica gel, mixtures of CH2Cl2 and MeOH-40:1, 20:1 or 9:1).

Reference： [1]Eibl, Christoph; Munoz, Lenka; Tomassoli, Isabelle; Stokes, Clare; Papke, Roger L.; Gündisch, Daniela [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 23, p. 7309 - 7329]

23
[ 762-04-9 ]
[ 539-47-9 ]
[ 55984-13-9 ]

Yield	Reaction Conditions	Operation in experiment
71%	With copper(ll) sulfate pentahydrate; oxygen In acetonitrile at 60℃; for 6h;	3.26 4.2 General procedure for the synthesis of β-ketophos-phonates General procedure: Starting from the alkenyl acids: alkenyl acids 1 (0.2mmol), H-phosphonates 2 (0.4mmol), and CuSO4·5H2O (10mol%) were dissolved in 4mL CH3CN at round-bottomed flask and stirred at 60°C for 6h in an air atmosphere. Starting from the alkenes: alkenes 4 (0.2mmol), H-phosphonates 2 (0.3mmol), and CuSO4·5H2O (10mol%) were dissolved in 4mL CH3CN at round-bottomed flask and stirred at 60°C for 3h in an air atmosphere. Then, CH3CN was evaporated, and the reaction mixture was quenched with water, followed by extraction with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. The crude product was purified by silica gel chromatography (petroleum ether: ethyl acetate=1:1) to give the desired product.
37 mg	With iron(III) chloride; copper(II) bis(trifluoromethanesulfonate); triethylamine In dimethyl sulfoxide at 70℃; for 8h; Schlenk technique;

Reference： [1]Chen, Xi; Chen, Xiaolan; Li, Xu; Qu, Chen; Qu, Lingbo; Bi, Wenzhu; Sun, Kai; Zhao, Yufen [Tetrahedron, 2017, vol. 73, # 17, p. 2439 - 2446]
[2]Zhou, Mingxin; Zhou, Yao; Song, Qiuling [Chemistry - A European Journal, 2015, vol. 21, # 30, p. 10654 - 10658]

24
[ 17150-62-8 ]
[ 539-47-9 ]
(E)-N-benzyl-N-(but-3-en-1-yl)-3-(furan-2-yl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 3-(fur-2-yl)crotonic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0℃; for 1h; Stage #2: N-benzyl-3-butenylamine In N,N-dimethyl-formamide at 20℃;
57%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; Inert atmosphere;	Preparation of starting substrates 8, method A. General procedure: Homoallylbenzylamine 7 (1.0 mmol) was added to a mixture of the corresponding carboxylic acid 5 (1.0 mmol), EDCI (1.5 mmol), HOBt (2.0 mmol) and triethylamine (2.0 mmol) in DCM (0.10 M). The mixture was stirred overnight at rt. The reaction mixture was then hydrolysed with H2O (20 mL) and extracted with DCM (3 × 15 mL). Collected organic fractions were dried over Na2SO4 and, after removal of the solvents the crude reaction mixture was purified by flash chromatography.

Reference： [1]Shcherbakova, Valeriya; Dibchak, Dmitry; Snisarenko, Mariya; Skalenko, Yevhen; Denisenko, Aleksandr V.; Kuznetsova, Anastasiia S.; Mykhailiuk, Pavel K. [Journal of Organic Chemistry, 2021, vol. 86, # 3, p. 2200 - 2209]
[2]Miró, Javier; Sánchez-Roselló, María; Sanz, Álvaro; Rabasa, Fernando; Del Pozo, Carlos; Fustero, Santos [Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 1486 - 1493]

25
[ 77-78-1 ]
[ 539-47-9 ]
[ 623-18-7 ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate In acetone at 50℃;

Reference： [1]Hartman, Tomáš; Cibulka, Radek [Organic Letters, 2016, vol. 18, # 15, p. 3710 - 3713]

26
[ 1189-24-8 ]
[ 539-47-9 ]
diisobutyl (2-(furan-2-yl)-2-oxoethyl)phosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With copper(ll) sulfate pentahydrate; oxygen In acetonitrile at 60℃; for 6h;	3.27 4.2 General procedure for the synthesis of β-ketophos-phonates General procedure: Starting from the alkenyl acids: alkenyl acids 1 (0.2mmol), H-phosphonates 2 (0.4mmol), and CuSO4·5H2O (10mol%) were dissolved in 4mL CH3CN at round-bottomed flask and stirred at 60°C for 6h in an air atmosphere. Starting from the alkenes: alkenes 4 (0.2mmol), H-phosphonates 2 (0.3mmol), and CuSO4·5H2O (10mol%) were dissolved in 4mL CH3CN at round-bottomed flask and stirred at 60°C for 3h in an air atmosphere. Then, CH3CN was evaporated, and the reaction mixture was quenched with water, followed by extraction with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. The crude product was purified by silica gel chromatography (petroleum ether: ethyl acetate=1:1) to give the desired product.

Reference： [1]Chen, Xi; Chen, Xiaolan; Li, Xu; Qu, Chen; Qu, Lingbo; Bi, Wenzhu; Sun, Kai; Zhao, Yufen [Tetrahedron, 2017, vol. 73, # 17, p. 2439 - 2446]

27
[ 5407-57-8 ]
[ 539-47-9 ]
(E)-N-(2-(7-chloroquinolin-4-ylamino)ethyl)-3-(furan-2-yl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: 3-(fur-2-yl)crotonic acid With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 5℃; for 0.25h; Stage #2: N-(7-chloroquinolin-4-yl)ethylenediamine With benzotriazol-1-ol In tetrahydrofuran at 0 - 5℃; for 1.5h;	4.4 General synthetic procedure for cinnamoyl compounds (9-14) General procedure: To the substituted cinnamic acid (1.0eq) derivatives (3-8) 15ml of tetrahydrofuran was added and cooled to 0-5°C, to this cooled solution 1.0eq of dicyclohexyl dicarbodimide (DCC) was added and stirred for 15min. Then (1.0eq of N-hydroxy benzo triazine) HOBT was added, stirred for 30 min and the solution of compound-2 (1.1eq) was added at 0-5°C for 60 min. The resulted mixture was maintained overnight at 25-30°C and the reaction was monitored by TLC. After completion of reaction the reaction mass was quenched into cold water 40ml and extracted with dichloro methane 2×25ml. The organic layer was dried with sodium sulfate, concentrated under high vacuum, charged into 10ml THF and kept at 0-5°C over night. The resulted solid was filtered under vacuum and also dried under vacuum at 45°C for 5h to obtain dried solid compound.

Reference： [1]Gayam, Venkatareddy; Ravi, Subban [European Journal of Medicinal Chemistry, 2017, vol. 135, p. 382 - 391]

28
[ 284462-37-9 ]
[ 539-47-9 ]
(E)-4-(4-(3-(furan-2-yl)acrylamido)phenoxy)-N-methylpicolinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 25℃; for 12h;	11 Example 11 (0139) (E)-4-(4-(3-(furan-2-yl)acrylamido)phenoxy)-N-methylpicolinamide (7b) Example 11 (0139) (E)-4-(4-(3-(furan-2-yl)acrylamido)phenoxy)-N-methylpicolinamide (7b) (0140) To a solution of (E)-3-(furan-2-yl)acrylic acid (69 mg, 0.5 mmol) in dry dimethylformamide, EDCI (115 mg, 0.6 mmol) and HOBT (81 mg, 0.6 mmol) were added at 0 C and the reaction mixture was stirred for 20 min. To the reaction mixture 4-(4-aminophenoxy)-N-methylpicolinamide (121.5 mg, 0.5 mmol) was added and stirred at room temperature (25°C) for 12 h. The contents of the reaction mixture were poured into ice-cold water (25 mL), extracted with ethyl acetate (3X15.0) and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained residue was purified by column chromatography using ethyl acetate-hexane (0-50%) as eluent to give 127 mg (70%) of analytically pure compound (7b). mp: 163-165 °C ; 1H NMR (CDC13): δ 8.38 (d, = 5.64 Hz, 1H), 8.04 (d, = 4.42 Hz, 1H), 7.88 (s, 1H), 7.69 (d, = 2.28 Hz, 2H), 7.67 (s, 1H), 7.53 (d, = 15.10 Hz, 1H), 7.45 (s, 1H), 7.04 (d, J = 8.85 Hz, 2H), 6.96 (q, J = 2.59,5.64 Hz, 1H), 6.60 (d, J = 3.35 Hz , 1H), 6.49 (d, J = 14.95 Hz, 1H), 6.47 (d, J = 1.83 Hz, 1H), 3.02 (d, J = 5.18 Hz, 3H) ; MS (ESI): m/z 364 [M+H]+.

Reference： [1]Current Patent Assignee: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (IN) - WO2017/125946, 2017, A1 Location in patent: Page/Page column 26

29
decursinol [ No CAS ]
[ 539-47-9 ]
(7S)-(+)-3-(2-furanyl)acrylic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73.6%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 5h; Inert atmosphere;	1 Synthesis of SLCB050 [(7S)-(+)-3-(2-Furanyl)-acrylic acid, 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester] [Step 1] Under N2 gas, trans-3-(2-furanyl)acrylic acid (560 mg, 4.06 mmol, 1 eq), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC, 1.17 g, 6.09 mmol, 1.5 eq), and 4-(dimethylamino)pyridine (4-DMAP, 198 mg, 1.62 mmol, 0.4 eq) were added to a 100 mL round-bottom flask, and then, dissolved in anhydrous dichloromethane (100 ml). (S)-(+)-decursinol (1 g, 4.06 mmol, 1 eq, KR 0715206) was added to the mixed solution, followed by being stirred at room temperature for 5 hours and concentrated under reduced pressure. The filtrate was then separated by silica gel column (ethylacetate: n-hexane=gradient elution to 1:3 from 1:8), thereby obtaining (7S)-(+)-3-(2-furanyl)-acrylic acid, 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (SLCB050) having the following material properties: yield: 73.6%; orange solid-phase; mp: 96.1° C.: Rf=0.62 (n-hexane:ethyl acetate=1:1); [α]D25+62.4 (c=3, CHCl3); 1H NMR (400 MHz, CDCl3): δH 7.64 (1H, s, H-6'), 7.58 (1H, d, J=9.6 Hz, H-4), 7.56 (1H, d, J=16.0 Hz, H-3'), 7.41 (1H, d, J=1.6 Hz, H-7'), 7.17 (1H, s, H-5), 6.82 (1H, s, H-10), 6.55 (1H, d, J=1.6 Hz, H-8'), 6.23 (1H, d, J=9.6 Hz, H-3), 6.13 (1H, d, J=16.0 Hz, H-2'), 5.17 (1H, t, J=4.4 Hz, H-7), 3.23 (1H, dd, J=4.4, 17.6 Hz, H-6a), 2.92 (1H, dd, J=4.4, 17.6 Hz, H-6b), 1.42 (3H, s, CH3-8), 1.38 (3H, s, CH3-8); 13C NMR (100 MHz, CDCl3) δC 166.3 (C-1'), 161.3 (C-2), 156.3 (C-9a), 154.1 (C-10a), 144.8 (C-4'), 144.5 (C-6'), 143.1 (C-4), 135.8 (C-3'), 128.7 (C-5), 117.0 (C-2'), 115.6 (C-5a), 113.3 (C-3), 112.9 (C-7'), 112.9 (C-4a), 107.2 (C-8'), 104.7 (C-10), 76.6 (C-8), 70.0 (C-7), 27.8 (C-6), 24.8 (CH3-8), 23.3 (CH3-8); and ESI-MS: m/z=389 [M+Na]+.

Reference： [1]Current Patent Assignee: PUSAN NATIONAL UNIVERSITY - US2017/129904, 2017, A1 Location in patent: Paragraph 0129; 0130; 0131; 0132; 0133; 0134

30
[ 539-47-9 ]
[ 477533-63-4 ]
C₁₈H₁₇NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h;	Methyl (S)-[(E,E)-2-Hexa-2,4-dienoyl]-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (6) General procedure: Sorbic acid(1.30 g, 11.6 mmol) and EDC·HCl (2.59 g, 13.5 mmol) wereadded to a solution of compound 438) (2.00 g, 9.65 mmol) inCH2Cl2 (30 mL), and the reaction mixture was stirred at roomtemperature for 2 h. The reaction mixture was washed withsaturated NaHCO3 solution and then dried over Na2SO4. Thesolvent was removed under reduced pressure. The residueobtained was purified by column chromatography to give 6(2.71 g, 90% yield) as a colorless oil.

Reference： [1]Morishita, Ko; Shoji, Yoshimichi; Fukui, Masaki; Ito, Yuma; Kitao, Tatsuya; Ozawa, Shin-ichiro; Hirono, Shuichi; Shirahase, Hiroaki [Chemical and Pharmaceutical Bulletin, 2018, vol. 66, # 12, p. 1131 - 1152]

31
[ 93930-15-5 ]
[ 539-47-9 ]
((1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(furan-2-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 8h; Inert atmosphere;	4.1.5. General procedure for the synthesis of compounds 6a-6b, 6f-6g and 7a-7m General procedure: To a solution of compound 2 (53 mg, 0.2 mmol, 1 eq), EDCI (115 mg, 0.6 mmol, 2 eq), DMAP (1.2 mg, 0.01 mmol, 0.05 eq) and corresponded acid (0.3 mmol, 1.5 eq) in CH2Cl2 (2 mL) was added Et3N (83.4 mL, 0.6 mmol, 2 eq) at 0 °C. The mixture was stirred for 8 h at room temperature. The reaction was quenched with saturated aqueous NaHCO3 and extracted with CH2Cl2 (3 15 mL). The combined organic layers were washed with saturated brine, dried over Na2SO4, and concentrated to give an oily crude product, which was purified on a silica gel column to yield compound 6a-6b, 6f-6g and 7a-7m. 4.1.5.1. ((1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[20 ,3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(furan-2-yl)acrylate (6a). Colorless oil(yield: 82%). 1H NMR (400 MHz, CDCl3) d 7.48 (s, 1H, Ar-H), 7.42 (d,J 15.7 Hz, 1H, H-18), 6.62 (d, J 3.3 Hz, 1H, Ar-H), 6.47 (dd, J 3.2,1.7 Hz, 1H, Ar-H), 6.28 (d, J 15.7 Hz, 1H, H-18), 6.24 (d, J 3.4 Hz,1H, H-13), 5.72 (t, J 8.2 Hz, 1H, H-1), 5.55 (d, J 3.1 Hz, 1H, H-13),4.75 (d, J 12.6 Hz, 1H, H-14), 4.58 (d, J 12.6 Hz, 1H, H-14), 3.86 (t,J 9.3 Hz, 1H, H-6), 3.01e2.91 (m, 1H, H-7), 2.88 (d, J 9.4 Hz, 1H,H-5), 2.47e2.13 (m, 6H, CH2), 1.72e1.63 (m, 1H, CH2), 1.54 (s, 3H, H-15), 1.11 (t, J 12.7 Hz, 1H, CH2). 13C NMR (100 MHz, CDCl3)d 169.3(C-12), 166.6(C-16), 150.5(Ar-C), 145.0(Ar-C), 138.6(C-11),134.9(C-10), 131.6(C-1), 130.5(C-18), 120.3(C-13), 115.3(C-17),114.8(Ar-C), 112.3(Ar-C), 80.9(C-6), 66.7(C-14), 63.2(C-5), 59.9(C-4),42.6(C-7), 36.5(C-3), 25.7(C-8), 24.4(C-9), 23.7(C-2), 17.9(C-15).HRMS (ESI) calcd for C22H28NO6 [M NH4] 402.1911, found402.1910.

Reference： [1]Ge, Weizhi; Hao, Xin; Han, Fangzhi; Liu, Zhongquan; Wang, Tianpeng; Wang, Mengmeng; Chen, Ning; Ding, Yahui; Chen, Yue; Zhang, Quan [European Journal of Medicinal Chemistry, 2019, vol. 166, p. 445 - 469]

32
[ 5033-28-3 ]
[ 539-47-9 ]
4-chloro-N'-[(2E)-3-(furan-2-yl)prop-2-enoyl]oxy}benzenecarboximidamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: 3-(fur-2-yl)crotonic acid With chloroformic acid ethyl ester; triethylamine In 1,4-dioxane at 20℃; for 0.25h; Stage #2: 4-chlorobenzamidoxime In 1,4-dioxane at 20℃; for 0.25h;	Synthesis and characterization of O-acylamidoximes 3a-p General procedure: Method A. An ethyl chloroformate (ECF, 3.0 mmol, 0.29 mL) was added, dropwise to a mixture of carboxylic acid (2.5 mmol) and TEA (3.0 mmol, 0.42 mL) in 1,4-dioxane (4 mL). The reaction mixture was stirred at room temperature for 15 min. An amidoxime 2 (2.5 mmol) in 1,4-dioxane (4 mL) was added and resulted mixture was stirred at room temperature for 15 min. The solvent was evaporated at reduced pressure and residue was diluted with water (25 mL). The precipitate was filtered off, washed with cold water (25 mL) and dried in air at room temperature.

Reference： [1]Tarasenko, Marina; Sidneva, Vera; Belova, Alexandra; Romanycheva, Anna; Sharonova, Tatyana; Baykov, Sergey; Shetnev, Anton; Kofanov, Eugeniy; Kuznetsov, Mikhail A. [Arkivoc, 2018, vol. 2018, # 7, p. 458 - 470]

33
[ 67-68-5 ]
[ 539-47-9 ]
(E)-(methylthio)methyl 3-(furan-2-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With triethylamine at 170℃; for 20h; Schlenk technique; Inert atmosphere; Green chemistry;	Typical procedure for the synthesis of MTM ester General procedure: An oven-dried Schlenk tube equipped with a stir bar was charged with carboxylic acid (0.2 mmol) and Et3N (28 mL, 0.2 mmol, 1 equiv). The tube was fitted with a rubber septum, and then it was evacuated and refilled with nitrogen three times. Under nitrogen, DMSO (2 mL) was added via syringe. The rubber septum was replaced with a Teflon screwcap under nitrogen flow, and the Schlenk tube was pressurized to 1 atm. With stirring, the reaction mixtures were heated at 160 C for the indicated amount of time (unless otherwise specified). After cooling to room temperature, the reaction mixture swere diluted with ether (10 mL) and filtered through a pad of silica gel that was then washed with ether (10 mL X 3). The combined organic phase was washed with brine (20 mL 2), dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified by flash column chromatography over silica gel to provide the corresponding product with ethyl acetate/hexane as eluent.

Reference： [1]Wang, Shuiliang; Fu, Zhengjiang; Jiang, Yongqing; Liang, Yuxiang; Cai, Hu [Synthetic Communications, 2019, vol. 49, # 7, p. 950 - 958]

34
[ 137-26-8 ]
[ 539-47-9 ]
[ 111252-81-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	In 1,2-dichloro-ethane at 100℃; for 48h; Sealed tube;
91%	In 1,2-dichloro-ethane at 90 - 100℃; Schlenk technique;	19.1-19.2 Take 0.5 mmol of 3- (2-furyl) acrylic acid and 0.55 mmol of tetramethylthiuram disulfide into 0.5 to 1 ml of dichloroethane to make a mixture,Place the mixture in a 5ml Schlenk tube,Place in an oil bath at 90 100 , heat it for 36 48h, then cool to room temperature,Get the reaction solution;(2) The reaction solution obtained in step (1) is directly concentrated to obtain a concentrate,The concentrate was made with ethyl acetate / petroleum ether = 3/1 (v / v) as the developing agent,TLC separation was performed to obtain 75.1 mg of the target product.

Reference： [1]Lai, Miao; Wu, Zhiyong; Su, Fangyao; Yu, Yujian; Jing, Yanqiu; Kong, Jinmin; Wang, Zhenteng; Wang, Shuai; Zhao, Mingqin [European Journal of Organic Chemistry, 2020, vol. 2020, # 2, p. 198 - 208]
[2]Current Patent Assignee: HENAN AGRICULTURAL UNIVERSITY - CN111018735, 2020, A Location in patent: Paragraph 0148-0154

35
[ 97-77-8 ]
[ 539-47-9 ]
[ 88312-33-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	In 1,2-dichloro-ethane; at 90 - 100℃;Schlenk technique;	Add 0.5 mmol of 3- (2-furyl) acrylic acid and 0.55 mmol of tetraethylthiuram disulfide to 0.5 to 1 ml of dichloroethane to make a mixture,Place the mixture in a 5ml Schlenk tube,Put it in an oil bath at 90 100 , after 36 48h reaction,Cool to room temperature to obtain the reaction solution;(2) The reaction solution obtained in step (1) is directly concentrated to obtain a concentrate,The concentrate was made with ethyl acetate / petroleum ether = 2/1 (v / v) as the developing agent,TLC separation gave 48.3 mg of target product.

Reference： [1]European Journal of Organic Chemistry,2020,vol. 2020,p. 198 - 208
[2]Patent: CN111018735,2020,A .Location in patent: Paragraph 0239-0245

36
[ 539-47-9 ]
[ 90321-71-4 ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: 3-(fur-2-yl)crotonic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; Stage #2: With hydrazine hydrate monohydrate In cyclohexane; acetonitrile at 0 - 20℃; for 0.25h;	4.3. Synthesis of substituted aromatic acrylohydrazides (2a-2d) General procedure: The acid (1 equiv.) was dissolved in CH3CN (15ml) and to this solution, HOBt (1.2 equiv.) was added in one portion followed by addition of EDC. HCl(1.2 equiv.). The resultant mixture was stirred at room temperature and TLC monitoring was done to check the progress of the reaction, until the acid completely consumed in the reaction mixture. The resulting mixture was then slowly added to a solution of hydrazine (2 equiv.) and cyclohexene (1ml) in CH3CN (20ml) while the temperature was maintained at 0-5°C. The resultant mixture was stirred for 15min. After completion of the reaction, acetonitrile was removed under vacuum. Then reaction mixture was extracted with EtOAc and passed over anhydrous sodium sulfate. The crude compound was adsorbed and loaded on to the silica gel (100-200 mesh) column, and compound was eluted with (25-45%) ethyl acetate in hexane to give pure compounds with 63-79% yield.

Reference： [1]Kumar, Gautam; Goutami Godavari, Ambati; Tambat, Rushikesh; Kumar, Siva; Nandanwar, Hemraj; Elizabeth Sobhia; Jachak, Sanjay M. [Bioorganic Chemistry, 2020, vol. 104]

37
C₁₂H₁₄N₄O₃ [ No CAS ]
[ 539-47-9 ]
C₁₉H₁₆N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20.5%	Stage #1: C₁₂H₁₄N₄O₃ With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dimethyl sulfoxide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 3-(fur-2-yl)crotonic acid In dimethyl sulfoxide at 20℃; for 18h; Inert atmosphere; Stage #3: With potassium hydroxide In dimethyl sulfoxide at 20℃; for 4h; Inert atmosphere;	1 Compound I-12 (50mg, 0.23mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (48mg, 0.25mmol) was dissolved in dimethyl sulfoxide (1ml )in,Stir at room temperature under nitrogen protection for 30min, add (E)-3-(furan-2-yl)acrylic acid (31.4mg, 0.23mmol) to the reaction solution, continue to stir at room temperature for 18h,KOH (12.7 mg, 0.23 mmol) was added to the reaction solution and stirring was continued at room temperature for 4 hours.After monitoring the completion of the reaction, add an appropriate amount of water to the reaction solution,The product YLJ364 (15 mg, yield 20.5%) was obtained by suction filtration.

Reference： [1]Current Patent Assignee: JIANGNAN UNIVERSITY; Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - CN111848599, 2020, A Location in patent: Paragraph 0125; 0155; 0158

38
[ 100-02-7 ]
[ 539-47-9 ]
(E)-4-nitrophenyl 3-(furan-2-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With oxalyl dichloride; N-ethyl-N,N-diisopropylamine; N,N-dimethyl-formamide In dichloromethane at 20 - 25℃; for 1h;	General Procedure 2 General procedure: To a solution of corresponding carboxylic acid (1 equiv) in CH2Cl2 was added oxalyl chloride (1 equiv) and a few drops of DMF. The resulting reaction mixture was stirred for 1 hour at room temperature. Diisopropylethylamine (2 equiv) and the requisite aryl alcohol (1 equiv) were added and the mixture was stirred overnight at room temperature. The solvent was removed in vacuo and the residue was purified by column chromatography under the conditions specified to afford the final product.

Reference： [1]Smith, Andrew D.; Wu, Jiufeng; Young, Claire M. [Tetrahedron, 2021, vol. 78]

39
6-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-amine [ No CAS ]
[ 539-47-9 ]
(E)-N-(6-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-yl)-3-(furan-2-yl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25.2%	Stage #1: 3-(fur-2-yl)crotonic acid With pyridine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In 1-methyl-pyrrolidin-2-one at 20℃; for 0.166667h; Stage #2: 6-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-amine In 1-methyl-pyrrolidin-2-one at 120℃; for 2h; Microwave irradiation;	70 (E)-N-(6-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-yl)-3-(furan-2-yl)acrylamide A solution of (2E)-3-(furan-2-yl)prop-2-enoic acid (214 mg, 1.55 mmol), HATU (589 mg, 1.55 mmol), and pyridine (0.2 mL) in NMP (10 mL) was stirred at room temperature for 10 min. It was added 6-{7H-pyrrolo[2,3-d]pyrimidin-7-yl}pyridin-2-amine (55 mg, 0.260 mmol) and stirred in microwave at 120°C for 2 h. It was purified with reverse phase column (0.01% ammonia and ammonium bicarbonate in water and acetonitrile) to give (E)-N-(6-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-yl)-3-(furan-2-yl)acrylamide as a white solid. Yield: (19.9 mg, 25.2%). ES-MS [M+H]+: 332.1 (Method-E). NMR (400 MHz, DMSO-de): d 10.9 (1H, s), 9.18 (1H, s), 8.99 (1H, s), 8.43 (1H, d, J=7.6 Hz), 8.38 (1H, d, J=4.0 Hz), 8.19 (1H, d, J=8.4 Hz), 8.08 (1H, t, J=8.0 Hz), 7.87 (1H, s), 7.49 (1H, d, J=15.6 Hz), 6.96 (1H, d, J=4.0 H), 6.91 (1H, d, J=3.2 Hz), 6.85 (1H, d, J=15.6 Hz), 6.66-6.45 (1H, m).

Reference： [1]Current Patent Assignee: GAIN THERAPEUTICS - WO2021/105906, 2021, A1 Location in patent: Page/Page column 113; 114

40
4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-amine [ No CAS ]
[ 539-47-9 ]
(E)-N-(4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-yl)-3-(furan-2-yl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44.1%	Stage #1: 3-(fur-2-yl)crotonic acid With pyridine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In 1-methyl-pyrrolidin-2-one at 20℃; for 0.166667h; Stage #2: 4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-amine In 1-methyl-pyrrolidin-2-one at 120℃; for 2h; Microwave irradiation;	71 (E)-N-(4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyridin-2-yl)-3-(furan-2-yl)acrylamide A solution of (2E)-3-(furan-2-yl)prop-2-enoic acid (392 mg, 2.80 mmol), HATU (1.06 g, 2.8 mmol), diisopropylethylamine (361 mg, 200 mg) and pyridine (0.2 mL) in NMP (10 mL) was stirred at room temperature for 10 min. It was added 6-{7H-pyrrolo[2,3- d]pyrimidin-7-yl}pyridin-2-amine (100 mg, 0.47 mmol). The mixture was stirred in microwave at 120°C for 2 h. It was purified with reverse phase colunm (C18, 0.01% ammonia and ammonium bicarbonate in water and acetonitrile) to give (E)-N-(4-(7H- pyrrolo[2,3-d]pyrimidin-7-yl) pyridin-2-yl)-3-(furan-2-yl)acrylamide as a white solid. Yield: (68.6 mg, 44.1%). ES-MS [M+H]+: 332.1 (Method-E). NMR (400 MHz, DMSO-de): d 10.9 (1H, s),9.18 (1H, s), 9.05 (1H, d, J=2.0Hz), 8.97 (1H, s), 8.49 (1H, d, J=5.2 Hz), 8.18 (1H, d, J=4.0 Hz), 7.86 (1H, d, J=1.6 Hz), 7.80 (1H, dd, J=2.0, 2.0 Hz), 7.49 (1H, d, J=15.2 Hz), 6.98 (1H, d, J=3.6 H), 6.90 (1H, d, J=3.6 Hz), 6.85 (1H, d, J=15.6 Hz), 6.65 (1H, dd, J=1.6, 2.0 Hz).

Reference： [1]Current Patent Assignee: GAIN THERAPEUTICS - WO2021/105906, 2021, A1 Location in patent: Page/Page column 114; 115

41
[ 622-79-7 ]
[ 539-47-9 ]
1-benzyl-4-(furan-2-yl)-1H-1,2,3-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With piperidine In neat (no solvent) at 110℃; for 14h;	General Procedure for the synthesis of 1,4-disubstituted-1,2,3-triazole (3a-3u) A mixture of cinnamic acid (1, 1.0 mmol), organic azides (2, 1.5 mmol), piperidine (0.5 mmol) was heated at 110 °C for 14h. Completion of the reaction was monitored by TLC and the reaction mixture was cooled to room temperature and purified by column chromatography.

Reference： [1]Rengasamy; Vijayalakshmi; Punitha; Paul Raj; Karthikeyan; Elangovan [Tetrahedron Letters, 2021, vol. 84]

42
(4aR,5S,6S,6aR,9S,11aS,11bR,14R)-5,6,14-trihydroxy-4,4-dimethyl-8-methylene-4,4a,5,6,9,10,11,11a-octahydro-3H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-7(8H)-one [ No CAS ]
[ 539-47-9 ]
(4aR,5S,6S,6aR,9S,11aS,11bR,14R)-5,6-dihydroxy-4,4-dimethyl-8-methylene-7-oxo-4,4a,5,6,7,8,9,10,11,11a-decahydro-3H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl (E)-3-(furan-2-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃;	4.2.3. (5S,6S,6aR,9S,11bR,14R)-5,6-dihydroxy-4,4-dimethyl-8-methylene-7-oxodo-decahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl cyclohexanecarboxylate(16b) General procedure: Compound 14 (0.086 mmol) and cyclohexane carboxylic acid(0.129 mmol) were dissolved in anhydrous dichloromethane(10 mL), 0.16 mmol of 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDCI) and catalytic amount ofDMAP was added. The solution was stirred at room temperatureuntil compound 14 was disappear. Then, the solution was dilutedby saturated sodium bicarbonate water solution, and was extractedwith ethyl acetate for three times. The combined organic phaseswere washed with brine, dried over anhydrous sodium sulfate, andconcentrated in vacuo. The residue was subjected to columnchromatography (silica gel, ethyl acetate/petroleum ether, 1:8) toobtain compound 16b (86% yield).
63%	With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃;	4.2.3. (5S,6S,6aR,9S,11bR,14R)-5,6-dihydroxy-4,4-dimethyl-8-methylene-7-oxodo-decahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl cyclohexanecarboxylate(16b) General procedure: Compound 14 (0.086 mmol) and cyclohexane carboxylic acid(0.129 mmol) were dissolved in anhydrous dichloromethane(10 mL), 0.16 mmol of 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDCI) and catalytic amount ofDMAP was added. The solution was stirred at room temperatureuntil compound 14 was disappear. Then, the solution was dilutedby saturated sodium bicarbonate water solution, and was extractedwith ethyl acetate for three times. The combined organic phaseswere washed with brine, dried over anhydrous sodium sulfate, andconcentrated in vacuo. The residue was subjected to columnchromatography (silica gel, ethyl acetate/petroleum ether, 1:8) toobtain compound 16b (86% yield).

Reference： [1]Chen, Zhe-Sheng; Du, Pian; Liu, Junkai; Shao, Xiao; Wu, Hongyu; Xie, Shaowen; Xu, Jinyi; Xu, Shengtao; Xue, Songtao; Yang, Dong-Hua; Yao, Hong [European Journal of Medicinal Chemistry, 2022, vol. 231]
[2]Chen, Zhe-Sheng; Du, Pian; Liu, Junkai; Shao, Xiao; Wu, Hongyu; Xie, Shaowen; Xu, Jinyi; Xu, Shengtao; Xue, Songtao; Yang, Dong-Hua; Yao, Hong [European Journal of Medicinal Chemistry, 2022, vol. 231]

43
(6R,6aR,9S,11bS,14R)-6,14-dihydroxy-4,4-dimethyl-8-methylene decahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-7(8H)-one [ No CAS ]
[ 539-47-9 ]
(6R,6aR,9S,11bS,14R)-6-hydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl (E)-3-(furan-2-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃;	4.2.3. (5S,6S,6aR,9S,11bR,14R)-5,6-dihydroxy-4,4-dimethyl-8-methylene-7-oxodo-decahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl cyclohexanecarboxylate(16b) General procedure: Compound 14 (0.086 mmol) and cyclohexane carboxylic acid(0.129 mmol) were dissolved in anhydrous dichloromethane(10 mL), 0.16 mmol of 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDCI) and catalytic amount ofDMAP was added. The solution was stirred at room temperatureuntil compound 14 was disappear. Then, the solution was dilutedby saturated sodium bicarbonate water solution, and was extractedwith ethyl acetate for three times. The combined organic phaseswere washed with brine, dried over anhydrous sodium sulfate, andconcentrated in vacuo. The residue was subjected to columnchromatography (silica gel, ethyl acetate/petroleum ether, 1:8) toobtain compound 16b (86% yield).
48%	With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃;	4.2.3. (5S,6S,6aR,9S,11bR,14R)-5,6-dihydroxy-4,4-dimethyl-8-methylene-7-oxodo-decahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl cyclohexanecarboxylate(16b) General procedure: Compound 14 (0.086 mmol) and cyclohexane carboxylic acid(0.129 mmol) were dissolved in anhydrous dichloromethane(10 mL), 0.16 mmol of 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDCI) and catalytic amount ofDMAP was added. The solution was stirred at room temperatureuntil compound 14 was disappear. Then, the solution was dilutedby saturated sodium bicarbonate water solution, and was extractedwith ethyl acetate for three times. The combined organic phaseswere washed with brine, dried over anhydrous sodium sulfate, andconcentrated in vacuo. The residue was subjected to columnchromatography (silica gel, ethyl acetate/petroleum ether, 1:8) toobtain compound 16b (86% yield).

Reference： [1]Chen, Zhe-Sheng; Du, Pian; Liu, Junkai; Shao, Xiao; Wu, Hongyu; Xie, Shaowen; Xu, Jinyi; Xu, Shengtao; Xue, Songtao; Yang, Dong-Hua; Yao, Hong [European Journal of Medicinal Chemistry, 2022, vol. 231]
[2]Chen, Zhe-Sheng; Du, Pian; Liu, Junkai; Shao, Xiao; Wu, Hongyu; Xie, Shaowen; Xu, Jinyi; Xu, Shengtao; Xue, Songtao; Yang, Dong-Hua; Yao, Hong [European Journal of Medicinal Chemistry, 2022, vol. 231]

44
[ 901925-05-1 ]
[ 15690-24-1 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
60%	With N-ethyl-N,N-diisopropylamine; O-(7-azabenzotriazol-1-yl)-n,n,n',n'-tetramethyluronium hexafluoro-phosphate In N,N-dimethyl-formamide at 20℃; for 16h;	General procedure for synthesis and spectral characterization of 10 (a-t) and 13 (a-g); General procedure: The corresponding amine (150 mg, 1 eq.), HATU (316 mg 1.2 eq.) and DIPEA (250 μl, 2 eq.) were added to the solution of cin- namic acids (1 eq.) in DMF (4 mL). The reaction mixture was al- lowed to stirr at room temperature. The progress of reaction was monitored by TLC. Upon completion, water (50 mL) was added and extracted by using EtOAc (3 ×50 mL). The organic layer was com- bined, dried over anhydrous Na 2 SO 4 , filtered and evaporated un- der reduce pressure. The crude product was triturated with diethyl ether to afford the desired solid products.

Reference： [1]Ganai, Ab Majeed; Pathan, Tabasum Khan; Merugu, Srinivas Reddy; Kozlanská, Karolína; Vojáčková, Veronika; Kryštof, Vladimír; Mokoena, Sithabile; Kayamba, Francis; Karpoormath, Rajshekhar [Journal of Molecular Structure, 2022, vol. 1267]

45
[ CAS Unavailable ]
[ 15690-24-1 ]
[ 381199-78-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With trifluorormethanesulfonic acid In dichloromethane at 0℃; for 2h;	4.4.3. General Procedure for Synthesis of 3-(furan-2-yl)-3-phenylpropanoic Acids andEsters 2a-r from Compounds 1 and Arenes in TfOH General procedure: To the mixture of compound 1 (0.36 mmol), arene (0.1 mL), and CH2Cl2 (1 mL) wasadded TfOH (0.5 mL, 6.45 mmol). The reaction mixture was stirred at 0 C for 2 h andpoured into water (50 mL) and extracted with chloroform (3 50 mL). The combinedextract was washed with water (3 50 mL) and dried over Na2SO4; the solvent wasdistilled under a reduced pressure

Reference： [1]Kalyaev, Mikhail V.; Ryabukhin, Dmitry S.; Borisova, Marina A.; Ivanov, Alexander Yu.; Boyarskaya, Irina A.; Borovkova, Kristina E.; Nikiforova, Lia R.; Salmova, Julia V.; Ul’yanovskii, Nikolay V.; Kosyakov, Dmitry S.; Vasilyev, Aleksander V. [Molecules, 2022, vol. 27, # 14]

46
[ CAS Unavailable ]
[ 15690-24-1 ]
[ 1534975-01-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With trifluorormethanesulfonic acid In dichloromethane at 0℃; for 2h;	4.4.3. General Procedure for Synthesis of 3-(furan-2-yl)-3-phenylpropanoic Acids andEsters 2a-r from Compounds 1 and Arenes in TfOH General procedure: To the mixture of compound 1 (0.36 mmol), arene (0.1 mL), and CH2Cl2 (1 mL) wasadded TfOH (0.5 mL, 6.45 mmol). The reaction mixture was stirred at 0 C for 2 h andpoured into water (50 mL) and extracted with chloroform (3 50 mL). The combinedextract was washed with water (3 50 mL) and dried over Na2SO4; the solvent wasdistilled under a reduced pressure

Reference： [1]Kalyaev, Mikhail V.; Ryabukhin, Dmitry S.; Borisova, Marina A.; Ivanov, Alexander Yu.; Boyarskaya, Irina A.; Borovkova, Kristina E.; Nikiforova, Lia R.; Salmova, Julia V.; Ul’yanovskii, Nikolay V.; Kosyakov, Dmitry S.; Vasilyev, Aleksander V. [Molecules, 2022, vol. 27, # 14]

47
[ 108-38-3 ]
[ 15690-24-1 ]
[ 1528524-03-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	With trifluorormethanesulfonic acid In dichloromethane at 0℃; for 2h;	4.4.3. General Procedure for Synthesis of 3-(furan-2-yl)-3-phenylpropanoic Acids andEsters 2a-r from Compounds 1 and Arenes in TfOH General procedure: To the mixture of compound 1 (0.36 mmol), arene (0.1 mL), and CH2Cl2 (1 mL) wasadded TfOH (0.5 mL, 6.45 mmol). The reaction mixture was stirred at 0 C for 2 h andpoured into water (50 mL) and extracted with chloroform (3 50 mL). The combinedextract was washed with water (3 50 mL) and dried over Na2SO4; the solvent wasdistilled under a reduced pressure

Reference： [1]Kalyaev, Mikhail V.; Ryabukhin, Dmitry S.; Borisova, Marina A.; Ivanov, Alexander Yu.; Boyarskaya, Irina A.; Borovkova, Kristina E.; Nikiforova, Lia R.; Salmova, Julia V.; Ul’yanovskii, Nikolay V.; Kosyakov, Dmitry S.; Vasilyev, Aleksander V. [Molecules, 2022, vol. 27, # 14]

48
[ 15690-24-1 ]
[ 108-67-8 ]
[ 1511008-46-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With trifluorormethanesulfonic acid In dichloromethane at 0℃; for 2h;	4.4.3. General Procedure for Synthesis of 3-(furan-2-yl)-3-phenylpropanoic Acids andEsters 2a-r from Compounds 1 and Arenes in TfOH General procedure: To the mixture of compound 1 (0.36 mmol), arene (0.1 mL), and CH2Cl2 (1 mL) wasadded TfOH (0.5 mL, 6.45 mmol). The reaction mixture was stirred at 0 C for 2 h andpoured into water (50 mL) and extracted with chloroform (3 50 mL). The combinedextract was washed with water (3 50 mL) and dried over Na2SO4; the solvent wasdistilled under a reduced pressure

Reference： [1]Kalyaev, Mikhail V.; Ryabukhin, Dmitry S.; Borisova, Marina A.; Ivanov, Alexander Yu.; Boyarskaya, Irina A.; Borovkova, Kristina E.; Nikiforova, Lia R.; Salmova, Julia V.; Ul’yanovskii, Nikolay V.; Kosyakov, Dmitry S.; Vasilyev, Aleksander V. [Molecules, 2022, vol. 27, # 14]

49
[ 15690-24-1 ]
[ CAS Unavailable ]
[ 4428-36-8 ]

Yield	Reaction Conditions	Operation in experiment
65%	With Aluminum Chloride In dichloromethane at 20℃; for 1h;	4.4.3. General Procedure for Synthesis of 3-(furan-2-yl)-3-phenylpropanoic Acids andEsters 2a-r from Compounds 1 and Arenes in TfOH General procedure: To the mixture of compound 1 (0.36 mmol), arene (0.1 mL), and CH2Cl2 (1 mL) wasadded TfOH (0.5 mL, 6.45 mmol). The reaction mixture was stirred at 0 C for 2 h andpoured into water (50 mL) and extracted with chloroform (3 50 mL). The combinedextract was washed with water (3 50 mL) and dried over Na2SO4; the solvent wasdistilled under a reduced pressure

Reference： [1]Kalyaev, Mikhail V.; Ryabukhin, Dmitry S.; Borisova, Marina A.; Ivanov, Alexander Yu.; Boyarskaya, Irina A.; Borovkova, Kristina E.; Nikiforova, Lia R.; Salmova, Julia V.; Ul’yanovskii, Nikolay V.; Kosyakov, Dmitry S.; Vasilyev, Aleksander V. [Molecules, 2022, vol. 27, # 14]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	15690-24-1	MDL No. :	MFCD11656544
Formula :	C₇H₆O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZCJLOOJRNPHKAV-ONEGZZNKSA-N
M.W :	138.12	Pubchem ID :	643402
Synonyms :

Num. heavy atoms :	10
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	35.38
TPSA :	50.44 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.28 cm/s

Log Po/w (iLOGP) :	1.36
Log Po/w (XLOGP3) :	1.21
Log Po/w (WLOGP) :	1.27
Log Po/w (MLOGP) :	0.02
Log Po/w (SILICOS-IT) :	1.09
Consensus Log Po/w :	0.99

[ CAS No. 15690-24-1 ] {[proInfo.proName]}

Quality Control of [ 15690-24-1 ]

Related Doc. of [ 15690-24-1 ]

Product Details of [ 15690-24-1 ]

Calculated chemistry of [ 15690-24-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 15690-24-1 ]

Application In Synthesis of [ 15690-24-1 ]

[ 15690-24-1 ] Synthesis Path-Downstream 1~49

Related Functional Groups of
[ 15690-24-1 ]

Alkenes

Carboxylic Acids

Related Parent Nucleus of
[ 15690-24-1 ]

Furans

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Log S (ESOL) :	-1.7
Solubility :	2.78 mg/ml ; 0.0201 mol/l
Class :	Very soluble
Log S (Ali) :	-1.87
Solubility :	1.88 mg/ml ; 0.0136 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.04
Solubility :	12.5 mg/ml ; 0.0902 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.33

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
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P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
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P270	Do not eat, drink or smoke when using this product.
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P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
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P334	Immerse in cool water/wrap n wet bandages.
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P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 15690-24-1 ] {[proInfo.proName]}

Quality Control of [ 15690-24-1 ]

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Product Details of [ 15690-24-1 ]

Calculated chemistry of [ 15690-24-1 ]

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Medicinal Chemistry

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[ 15690-24-1 ] Synthesis Path-Downstream 1~49

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Carboxylic Acids

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[ 15690-24-1 ]

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