Name: 10538-51-9|3-(2,5-Dimethoxyphenyl)acrylic acid|98%
Brand: Ambeed
SKU: A715826
Price: 19.0 USD
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1
[ 10538-51-9 ]
[ 10538-49-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With palladium 10% on activated carbon; hydrogen In ethyl acetate at 23℃; for 48h;	2,5-dimethoxyhydrocinnamic acid (13) To solution of 2,5-dimethoxycinnamic acid (50.0 g, 240.1 mmol, 1.0 eq) in dry EtOAc (500 ml, 0.48 M) was added 10% Pd/C (5.0 g, 10%wt) and treated with H2 condition at room temperature for 48 hours. The reaction mixture was filtered through a plug of celite with suction and the volatile components were removed under reduced pressure to leave pale-ivory-colored solid material 13 (50.1 g, 99%) without purification. Rf : 0.54 (EtOAc : Hexane = 1 : 1) 1H NMR (CDCl3, 400 MHz) : d 6.78-6.72 (m, 3H), 3.78 (s, 3H), 3.75 (s, 3H), 2.93-2.90 (t, J = 7.8 Hz, 2H), 2.68-2.64 (t, J = 7.8 Hz, 2H) 13C NMR (CDCl3, 100 MHz) : d 179.8, 153.4, 151.8, 129.7, 116.4, 111.7, 111.2, 55.8, 55.7, 34.1, 26.1 IR (neat, cm-1) : 2940, 2835, 1693, 1501, 1451, 1430, 1408, 1305, 1279, 1217, 1182, 1156, 1126, 1050, 1025, 936, 914, 864, 795, 731, 716, 682 LR/MS(m/z) [M+Na+] : 233.1
98%	With palladium 10% on activated carbon; hydrogen In ethyl acetate
95%	With hydrogen

95%	With borane-ammonia complex In methanol; water at 20℃; for 90h; chemoselective reaction;	4.5. General procedure for chemoselectivity reduction of , -unsaturated carbonyl compounds with Cu 50 Pd 50 /mpg-C 3 N 4 General procedure: The compounds 2, 4, 6, 8, 17, 19 and 22 are known. These compounds were synthesized according to literature [ 56 , 64 ]. Cu 50 Pd 50 /mpg-C 3 N 4 catalyst (5 mg) was suspended in water (3 mL) and MeOH (7 mL) mixture and it was sonicated for 5 min in a glass pressure tube. Then, convenient , -unsaturated car- bonyl compounds, and their derivatives (1 equiv.) and NH 3 BH 3 (1 equiv.) were added to the reaction mixture, respectively. The re- action mixture was stirred for 0.5 h at room temperature and the reaction was stopped. The catalyst was removed by filtration and then the solvent was removed under vacuum. The crude product was extracted with CH 2 CI 2 (2 ×15 mL). The combined extracts were dried over Na 2 SO 4 and the solvent was removed under vac- uum. Purification was performed through thin-layer chromatogra- phy (TLC) using EtOAc/hexane eluent on silica gel. Full experimen- tal detail, copies of 1 H, HRMS and 13 C NMR spectrum of all the compounds have been provided in the Supplementary file.
	With potassium hydroxide bei der elektrolytischen Reduktion;
	With palladium 10% on activated carbon; hydrogen

Reference： [1]Kim, Yun Yeong; Pyun, Yu Mi; Jeon, Bo Keun; Lee, Duck-Hyung [Bulletin of the Korean Chemical Society, 2018, vol. 39, # 5, p. 597 - 598]
[2]Mejlsoe, Soren L.; Christensen, Jorn B. [Journal of Heterocyclic Chemistry, 2014, vol. 51, # 4, p. 1051 - 1057]
[3]Baghdadchi, Jamil; Panetta, Charles A. [Journal of Organic Chemistry, 1983, vol. 48, # 21, p. 3852 - 3854]
[4]Bayrak, Cetin; Menzek, Abdullah; Sevim, Melike [Journal of Organometallic Chemistry, 2022, vol. 958]
[5]Fichter; Schlager [Helvetica Chimica Acta, 1927, vol. 10, p. 411]
[6]Kotha, Sambasivarao; Cheekatla, Subba Rao; Mandal, Binita [European Journal of Organic Chemistry, 2017, vol. 2017, # 29, p. 4277 - 4282]

2
[ 10538-51-9 ]
[ 33538-81-7 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium aluminium tetrahydride In tetrahydrofuran

Reference： [1]Glennon; Liebowitz; Mack [Journal of Medicinal Chemistry, 1978, vol. 21, # 8, p. 822 - 825]

3
[ 10538-51-9 ]
[ 123-31-9 ]
(+/-)-6-hydroxy-4-(2',5'-dimethoxyphenyl)-3,4-dihydrocoumarin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With boron trifluoride diethyl etherate; trichlorophosphate at 25 - 28℃;

Reference： [1]Singh, Ishwar; Prasad, Ashok K.; Sharma, Ajendra K.; Saxena, Rajendra K.; Olsen, Carl E.; Cholli, Ashok L.; Samuelson, Lynne A.; Kumar, Jayant; Watterson, Arthur C.; Parmar, Virinder S. [Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 4, p. 529 - 538]

4
[ 10538-51-9 ]
[ 108-46-3 ]
(+/-)-7-hydroxy-4-(2',5'-dimethoxyphenyl)-3,4-dihydrocoumarin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With boron trifluoride diethyl etherate; trichlorophosphate at 25 - 28℃;

Reference： [1]Singh, Ishwar; Prasad, Ashok K.; Sharma, Ajendra K.; Saxena, Rajendra K.; Olsen, Carl E.; Cholli, Ashok L.; Samuelson, Lynne A.; Kumar, Jayant; Watterson, Arthur C.; Parmar, Virinder S. [Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 4, p. 529 - 538]

5
[ 10538-51-9 ]
[ 6093-68-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With boron tribromide In 1,1-dichloroethane at 82℃; for 12h; Heating / reflux;	46 Equip a 5-L, three-neck, round-bottom flask with a large blade mechanical stirrer, thermocouple, an addition funnel, Claisen adapter, reflux condenser, and a sodium hydroxide scrubber. Charge the flask with 2,5-dimethoxycinnamic acid (182.3 g, 865 mmol, 1.0 equiv) and dichloroethane (2.5 L). Add boron tribromide (163. 5 ML, 433.2 g, 1.73 mol, 2.0 equiv. ) dropwise over 1 h, keeping the temperature below 35 oC. Gas evolution can be monitored as the temperature of the reaction is gradually increased to reflux (82 oC). Reflux for 12 h, cool to 5 oC, and quench by the careful addition of water (1.0 L). Filter the resulting yellow-red suspension/emulsion through a glass frit and wash with dichloroethane (1.0 L) and heptane (1.0 L) to afford a brown solid. Dry the wet material in a vacuum oven (30 in. , 35 oC) for 18 h, to afford the coumarin (180.3 g, 127% theory) as a brown solid : H NMR (300 MHz, DMSO-d6) 8 7.97 (d, J = 9.6 Hz, 1H), 7. 22 (d, J = 9.9 Hz, 1H), 7.05 (m, 2H), 6.43 (d, J = 9.6 Hz, 1H). Equip a 5-L, three-neck, round-bottom flask with a mechanical stirrer, thermocouple, an addition funnel, and an inlet adapter. Charge the flask with the coumarin prepared above (360.0 g, 2.20 mol, 1.0 equiv) and N, N-dimethylformamide (2.2 L). While keeping the temperature below 30 oC, add cesium carbonate [904.2 g, 2. 78 mol, 1. 25 equiv]. Then add benzyl bromide [475.5 g, 330.2 mL, 2.78 mol, 1.25 equiv] over a period of 1 h, keeping the temperature below 35 oC during the addition. Stir the mixture at ambient temperature (25-30 oC) for 10.5 h. Pour the reaction mixture into ice water (4.5 L), filter, and dry at ambient pressure for 72 H, TRITURATE in heptane (1.5 L) with vigorous stirring, filter, and dry under reduced pressure (30 in., 35 oC) to afford preparation 46 (302.4 g, 1.20 mol, 60%) as a light brown solid : H NMR (300 MHz, DMSO-D6) 8 7.99 (d, J = 9.6 Hz, 1H), 7.50-7. 29 (m, 8H), 6.49 (d, J = 9.5 Hz, 1H), 5.15 (S, 2H) ; 13C NMR (75 MHz, DMSO-D6) 8160. 0,154. 6,147. 9, 143. 9,136. 6,128. 4,127. 9, 127.7, 119.9, 119.1, 117.3, 116.6, 111.9, 69.8 ; IR (KBr) 3052 (w), 1708 (s), 1568 (m), 1492 (w), 1444 (w), 1383 (w), 1272 (m), 1168 (w), 1110 (m), 1020 (m), 927 (w), 814 (w), 762 (w), 709 (w) cm-1 ; HPLC analysis 95.9% (AUC), Phenomenex Luna C18 (2) column; ESI MS M/Z 253 [C6HIA03 + H] +
100%	With boron tribromide In 1,2-dichloro-ethane at 35 - 82℃; for 13h; Heating / reflux;	46 Equip a 5-L, three-neck, round-bottom flask with a large blade mechanical stirrer, thermocouple, an addition funnel, Claisen adapter, reflux condenser, and a sodium hydroxide scrubber. Charge the flask with 2,5-dimethoxycinnamic acid (182.3 g, 865 mmol, 1.0 equiv) and dichloroethane (2.5 L). Add boron tribromide (163.5 mL, 433.2 g, 1.73 mol, 2.0 equiv.) dropwise over 1 h, keeping the temperature below 35° C. Gas evolution can be monitored as the temperature of the reaction is gradually increased to reflux (82° C.). Reflux for 12 h, cool to 5° C., and quench by the careful addition of water (1.0 L). Filter the resulting yellow-red suspension/emulsion through a glass frit and wash with dichloroethane (1.0 L) and heptane (1.0 L) to afford a brown solid. Dry the wet material in a vacuum oven (30 in., 35° C.) for 18 h, to afford the coumarin (180.3 g, 127% theory) as a brown solid: 1H NMR (300 MHz, DMSO-d6) δ 7.97 (d, J=9.6 Hz, 1H), 7.22 (d, J=9.9 Hz, 1H), 7.05 (m, 2H), 6.43 (d, J=9.6 Hz, 1H).
55%	With phosphorus tribromide In dichloromethane

With boron tribromide In 1,1-dichloroethane at 40 - 83℃; for 22.5h; Heating / reflux;

12 Equip a 3-L, three-neck, round-bottom flask equipped with a large blade mechanical stirrer, a thermocouple, a Claisen adapter, an addition funnel, and a reflux condenser. Add 2,5-dimethoxycinnamic acid (102.8 g, 493 mmol, 1.0 equiv) and dichloroethane (1.5 L). Add boron tribromide (247.4 g, 987 mmol, 2.0 equiv) dropwise over 45 min while keeping the temperature below 40 oC. Rapidly stir the resulting mixture and heat gradually to 83 oC over 45 min, monitoring the temperature increase and gas evolution. Stir for 6 h at reflux then for 15 h at 76 oC. Cool the resulting mixture to room temperature and quenched carefully with water (450 mL). Filter the solid, wash with heptane and dry under vacuum to afford 6-hydroxy coumarin (95 g) as a light brown solid which is used without further purification. Equip a 2-L, three-neck, round-bottom flask with a magnetic stir bar and a thermocouple. Add 6-hydroxy coumarin (39. 8 g, 245 mmol, 1.0 equiv), anhydrous acetonitrile (700 mL) and N, N-diisopropylethylamine (200 mL, 1.15 mol, 4.7 equiv). Add chloromethyl methyl ether (40.0 mL, 527 mmol, 2.1 equiv) dropwise over 30 min while keeping the temperature below 40 oC. Stir the resulting mixture at room temperature for 3 h, then add an additional equiv of chloromethyl methyl ether. Stir at room temperature for 15 h, then quench the reaction mixture with saturated aqueous ammonium chloride (500 mL) and extracted with ethyl acetate. Combine the organic extracts and dry over anhydrous magnesium sulfate, filter and concentrate under reduced pressure. Purify the residue by column chromatography on silica gel (30-50% ethyl acetate/heptane) to afford a light yellow solid. Suspend the solid in a mixture of ethyl ACETATE/HEPTANE (150 mL, 10: 90), filter and dry to afford 6- METHOXYMETHOXY coumarin 17a (25.6 g, 50%) as a white solid : H NMR (300 MHz, CDC13) 8 7. 70 (d, J=7. 8HZ, 1H), 7.30-7. 12 (M, 3H), 6.41 (d, J = 7. 8 HZ, 1H), 5.20 (s, 2H), 3.48 (s, 3H); 13C NMR (75 MHz, CDC13) 8 161.2, 154.0, 149.5, 143.5, 121.6, 119.6, 118.1, 117.3, 113.8, 95.3, 56.4 ; IR (KBr) 1714 (s), 1570 (s), 1491 (m), 1447 (m), 1266 (s), 1154 (s), 1070 (s), 1017 (s) CM~L ; ESI MS m/z 207 [CLLH004 + H] +.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2004/94400, 2004, A2 Location in patent: Page 82-83
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2006/194871, 2006, A1 Location in patent: Page/Page column 46
[3]Morita, Yuki; Tasaka, Takeyasu; Yamaguchi, Remuto; Okamoto, Hiroaki; Takenaka, Shunsuke [Molecular Crystals and Liquid Crystals, 2005, vol. 439, p. 209/[2075]-220/[2086]]
[4]Current Patent Assignee: ELI LILLY & CO - WO2004/94400, 2004, A2 Location in patent: Page 44-45

6
[ 141-82-2 ]
[ 93-02-7 ]
[ 10538-51-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	With piperidine; pyridine at 50 - 85℃; for 5h; Reflux;
92%	With piperidine; pyridine at 50℃; for 4.5h; Reflux;
85%	With piperidine; pyridine

75%	With piperidine; pyridine; hydrogenchloride In lithium hydroxide monohydrate Heating;
67.26%	With pyridine; ammonium acetate at 85℃; for 5h; Darkness;	15.2 Step 2: Preparation of 2,5-dimethoxyphenylacryloylpiperazine (IX15) In a 50 mL round bottom flask with a reflux condenser, 3.98 g (0.024 mol) of 2,5-dimethoxybenzaldehyde, 4.90 g (0.047 mol) of malonic acid, and 0.18 g (0.023 mol) of ammonium acetate were sequentially added. 16 mL of pyridine was placed on an oil bath and heated to 85 ° C. The reaction was carried out under reflux for 5 h in the dark. The reaction was stopped, left to cool to room temperature, and poured into 50 mL of ice water. The pH was adjusted to about 2 with dilute hydrochloric acid, and a large amount of solid was precipitated. The solid was filtered by suction, and the solid was washed with water until it had no pyridine smell. Dry to obtain a solid product. Recrystallization using anhydrous ethanol to obtain VI15 as a white solid with a yield of 67.26% and a melting point of 147.3-147.4 ° C.
	With piperidine In ethanol for 6h;
	With piperidine; pyridine for 6h; Reflux;	3.2. General Procedure for the Synthesis of I General procedure: A mixture of benzaldehyde (30 mmol), malonic acid (120 mmol), and piperidine (2 mL) in pyridine was refluxed in a 250 mL single neck round bottomed flask (SNRB) for 6 h. Upon completion, the reaction mixture was poured into a 1 L Erlenmeyer flask (EF) containing cold, dilute HCl (200 mL) and stirred for 10 min. The resulting precipitate was filtered and washed with cold water to afford I.
	With piperidine; pyridine for 20h; Reflux;	5.10 General procedure for the preparation of compounds 8a-n General procedure: To the mixture of substituted benzaldehydes 7a-n (2.5mmol), pyridine (20.0mL), piperidine (0.2mL), propanedioic acid (5.0mmol) was added at room temperature and the mixture was heated and refluxed for 20h and monitored by TLC. The reaction mixture was cooled to room temperature and the solution was acidified to pH=5 to yielding a precipitate. The mixture was filtered and washed with water to furnish the compounds 8a-n.
	With pyridine; ammonium acetate at 85℃; for 5h;
	With piperidine; pyridine at 90℃; for 3h;	2.1.1. General procedure for the synthesis of compound CA-1 ~ CA-18 General procedure: The substituted cinnamic acids were synthesized using DoebnerKnoevenagel modification. Substituted benzaldehydes (10 mmol)malonic acid (12 mmol), and piperidine (1.2 mmol) were dissolved inpyridine (10 mL), the reaction mixture was heated at 90 C. After stirringfor 3 h, the mixture was concentrated in vacuo to remove thepyridine. The pH was adjusted to 1 with HCl/wether 1:2 (v/v). Theprecipitate was collected by filtration, and the filter cake was washedwith water and dried to afford compounds CA-1 ~ CA-18 as solids thatrequired no further purification.

Reference： [1]Chaaban, Ibrahim; El Khawass, El Sayeda M.; Mahran, Mona A.; Abd El Razik, Heba A.; El Salamouni, Nehad S.; Abdel Wahab, Abeer E. [Medicinal Chemistry Research, 2013, vol. 22, # 8, p. 3760 - 3778]
[2]Mejlsoe, Soren L.; Christensen, Jorn B. [Journal of Heterocyclic Chemistry, 2014, vol. 51, # 4, p. 1051 - 1057]
[3]Morita, Yuki; Tasaka, Takeyasu; Yamaguchi, Remuto; Okamoto, Hiroaki; Takenaka, Shunsuke [Molecular Crystals and Liquid Crystals, 2005, vol. 439, p. 209/[2075]-220/[2086]]
[4]Kotha, Sambasivarao; Cheekatla, Subba Rao; Mandal, Binita [European Journal of Organic Chemistry, 2017, vol. 2017, # 29, p. 4277 - 4282]
[5]Current Patent Assignee: WUHAN UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN110272412, 2019, A Location in patent: Paragraph 0168-0172
[6]Location in patent: experimental part Andreu, Gilberto L. Pardo; Inada, Natalia M.; Pellon, Rolando F.; Docampo, Maite L.; Fascio, Mirta L.; D'Accorso, Norma B.; Vercesi, Anibal E. [Arzneimittel-Forschung/Drug Research, 2009, vol. 59, # 4, p. 207 - 211]
[7]Leong, Sze Wei; Mohd Faudzi, Siti Munirah; Abas, Faridah; Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Wai, Lam Kok; Abdul Bahari, Mohd Nazri; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H. [Molecules, 2014, vol. 19, # 10, p. 16058 - 16081]
[8]Tu, Yuanbiao; Ouyang, Yiqiang; Xu, Shan; Zhu, Yan; Li, Gen; Sun, Chao; Zheng, Pengwu; Zhu, Wufu [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 7, p. 1495 - 1503]
[9]Gao, Cheng-Zhi; Dong, Wei; Cui, Zhi-Wen; Yuan, Qiong; Hu, Xia-Min; Wu, Qing-Ming; Han, Xianlin; Xu, Yao; Min, Zhen-Li [Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, vol. 34, # 1, p. 150 - 162]
[10]Bai, Yin-Peng; Deng, Nan; Li, Lei; Liu, Ying-Qian; Luo, Xiong-Fei; Ma, Yue; Xu, Chuan-Rui; Yang, Cheng-Jie; Zhang, Bao-Qi; Zhang, Mi; Zhang, Zhi-Jun; Zhou, Yong [Biochemical Pharmacology, 2022, vol. 200]

7
[ 10538-51-9 ]
[ 53138-44-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: LiAlH₄ / tetrahydrofuran 2: PBr₃ / benzene

Reference： [1]Glennon; Liebowitz; Mack [Journal of Medicinal Chemistry, 1978, vol. 21, # 8, p. 822 - 825]

8
[ 10538-51-9 ]
[3-(2,5-Dimethoxy-phenyl)-propyl]-dimethyl-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: LiAlH₄ / tetrahydrofuran 2: PBr₃ / benzene 3: ethanol

Reference： [1]Glennon; Liebowitz; Mack [Journal of Medicinal Chemistry, 1978, vol. 21, # 8, p. 822 - 825]

9
[ 136-95-8 ]
[ 10538-51-9 ]
[ 1162684-18-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2,5-dimethoxycinnamic acid With thionyl chloride at 45℃; for 1h; Stage #2: 2-amino-benzthiazole In chloroform for 2h;

Reference： [1]Location in patent: experimental part Andreu, Gilberto L. Pardo; Inada, Natalia M.; Pellon, Rolando F.; Docampo, Maite L.; Fascio, Mirta L.; D'Accorso, Norma B.; Vercesi, Anibal E. [Arzneimittel-Forschung/Drug Research, 2009, vol. 59, # 4, p. 207 - 211]

10
[ 10538-51-9 ]
[ 1038808-93-3 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride at 45℃; for 1h;
	With thionyl chloride Reflux;
	With oxalyl dichloride In dichloromethane for 3h;	1.2 General Procedure for the Synthesis of Substituted Cinnamoyl Chloride General procedure: Oxalyl chloride (1 ml) was added to the dichloromethane (10 ml) solutions of substituted cinnamic acid (2 mmol). The reaction mixture was stirred until the bubbling stopped (approximately 3 hours), and vaporized in vacuo. The cinnamoyl chloride was used directly without purification.

	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃;	5.11 General procedure for the preparation of compounds 9a-n General procedure: Oxalyl chloride (2.0mmol) was added drop-wise to a stirred mixture of compounds 8a-n (1.0mmol) and DMF (0.02mmol) in dichloromethane (16mL) in room temperature for 10min, and the mixture was distilled and dissolved in dichloromethane (16mL) immediately. The solution was used for the next step without further purification.
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide for 2h;
	With oxalyl dichloride; N,N-dimethyl-formamide at 0 - 20℃; for 1.5h;
	With oxalyl dichloride In N,N-dimethyl-formamide at 0 - 5℃; for 1h;	15.2 In a fume hood, add VI151.66 g (0.008 mol) to a 50 mL pear-shaped bottle, add 0.25 mL of N, N-dimethylformamide (DMF) dropwise, and cool to 0-5 ° C in an ice bath. Slowly add 2.00 mL (0.021 mol) of oxalyl chloride, and the addition is completed within 10 minutes. After dripping, the ice bath was removed, and the reaction was continued for 1 h until the solution was clear, and no gas was generated in the system. Use a rotary evaporator to evaporate the excess solvent and oxalyl chloride to obtain VII15. Add 16 mL of dichloromethane to dissolve it and seal it for later use.

Reference： [1]Location in patent: experimental part Andreu, Gilberto L. Pardo; Inada, Natalia M.; Pellon, Rolando F.; Docampo, Maite L.; Fascio, Mirta L.; D'Accorso, Norma B.; Vercesi, Anibal E. [Arzneimittel-Forschung/Drug Research, 2009, vol. 59, # 4, p. 207 - 211]
[2]Location in patent: body text Kim, Su Young; Shin, Sung Eui; Shin, Dong Myung [Molecular Crystals and Liquid Crystals, 2010, vol. 520, p. 116 - 121]
[3]Wang, Bo; Liu, Yang; Wang, Yanshi; Liu, Xin; Cheng, Mao-Sheng [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 23, p. 7110 - 7113]
[4]Tu, Yuanbiao; Ouyang, Yiqiang; Xu, Shan; Zhu, Yan; Li, Gen; Sun, Chao; Zheng, Pengwu; Zhu, Wufu [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 7, p. 1495 - 1503]
[5]Current Patent Assignee: INST OF HEMATOLOGY BLOOD DISEASES HOSPITAL OF CHIN; ACCENDA TECH; NANKAI UNIVERSITY - CN109206389, 2019, A Location in patent: Paragraph 0014
[6]Gao, Cheng-Zhi; Dong, Wei; Cui, Zhi-Wen; Yuan, Qiong; Hu, Xia-Min; Wu, Qing-Ming; Han, Xianlin; Xu, Yao; Min, Zhen-Li [Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, vol. 34, # 1, p. 150 - 162]
[7]Current Patent Assignee: WUHAN UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN110272412, 2019, A Location in patent: Paragraph 0168; 0173

11
[ 10538-51-9 ]
[ 1039359-99-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogen bromide; sodium nitrite In water; acetonitrile at 20℃; for 4h;	Representative procedure for bromodecarboxylation of α,β-unsaturated carboxylic acid (Table 1, entry 1) General procedure: In a stirred solution of cinnamic acid (0.3 gm, 2.0 mmol) in freshly distilled acetonitrile (10 mL) 48% aqueous solution of HBr (4.0 mmol) was added. To this reaction mixture was added aqueous solution of NaNO2 (20 mL, 2.5 M). The flask was immediately covered with an air filled balloon (1 L) and the stirring was continued at room temperature. After completion of the reaction (TLC), CHCl3 (10 mL) was added. The organic layer was separated and washed with aqueous solution of NaHCO3 (2 × 20 mL), followed by water (3 × 20 mL), finally dried over anhyd Na2SO4 and was concentrated in vacuum. The remaining residue was purified by column chromatography on silica gel (hexane/ethyl acetate = 9:1) to yield pure bromostyrene.

Reference： [1]Location in patent: experimental part Telvekar, Vikas N.; Takale, Balaram S. [Tetrahedron Letters, 2011, vol. 52, # 18, p. 2394 - 2396]

12
[ 10538-51-9 ]
[ 4559-70-0 ]
[ 1310329-68-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With copper(I) oxide; 1,10-Phenanthroline; silver(l) oxide In 1-methyl-pyrrolidin-2-one at 120℃; for 6h; Inert atmosphere; regioselective reaction;

Reference： [1]Hu, Jie; Zhao, Ning; Yang, Bin; Wang, Ge; Guo, Li-Na; Liang, Yong-Min; Yang, Shang-Dong [Chemistry - A European Journal, 2011, vol. 17, # 20, p. 5516 - 5521]

13
[ 71-23-8 ]
[ 10538-51-9 ]
n-propyl 2',5'-dimethoxycinnamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With sulfuric acid Reflux;	5.2.1. General procedure for the synthesis of the cinnamates 10-17 and 20-23 General procedure: A mixture of the commercially available cinnamic acid (4)/substituted cinnamic acids 1-3/dihydrocinnamic acids (18/19, 5 mmol) and the corresponding commercially available alcohols 5-9, i.e. propyl (7)/isopropyl (5)/octyl (8)/phenyl (6)/benzyl alcohol (9) (25 mL) and concentrated sulfuric acid (0.2 mL) was refluxed for 4-5 h (Scheme 1 and Scheme 2). On completion of the reactions as observed from TLC examination, the reaction mixture was neutralized by the addition of 10% aqueous sodium hydrogen carbonate solution (w/v) and then extracted with chloroform (2 × 25 mL), the combined organic layer was separated and dried over anhydrous Na2SO4. The crude product obtained after evaporation of organic solvent was loaded on a small silica gel column and eluted with chloroform to obtain the pure esters in 71-99% yields. The structures of all the cinnamates 10-17 and 20-23 were unambiguously established on the basis of their spectral (IR, 1H NMR, 13C NMR spectra and HRMS) analysis. The structures of the known esters 11, 16 and 17 were further confirmed by comparison of their melting points with those reported in the literature [27] and [28] (Table 5).

Reference： [1]Location in patent: experimental part Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh; Prasad, Ashok K.; Van Der Eycken, Erik; Olsen, Carl E.; Depass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram [European Journal of Medicinal Chemistry, 2011, vol. 46, # 11, p. 5498 - 5511]

14
[ 10538-51-9 ]
[ 107-03-9 ]
S-propyl 2',5'-dimethoxythiocinnamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With polyphosphate ester at 20℃;	5.3. Synthesis of the thiocinnamates 29-44 General procedure: A mixture of the commercially available carboxylic acids (1, 2, 4 and 18, 3 mmol), the appropriate commercially available thiol (24-28, 3.1 mmol) and polyphosphate ester (PPE, 2 mL) was stirred at room temperature for 0.5-11 h (refPreviewPlaceHolderScheme 3 and refPreviewPlaceHolderScheme 4). After completion of the reaction, the mixture was treated with saturated aqueous sodium hydrogen carbonate solution (20 mL) and extracted with chloroform (3 × 20 mL). The combined chloroform extract was dried over sodium sulfate and evaporated in a rotary vacuum evaporator. The crude compounds were passed through a silica-gel column, using pure petroleum ether as eluent, the desired compounds were obtained as colorless viscous oils in 92-98% yields. The structures of all the thio esters were unambiguously established on the basis of their spectral (IR, 1H NMR, 13C NMR spectra and HRMS) analysis. The structure of the known esters 38-41 were further confirmed by comparison of their melting points with those reported in the literature [29], [30], [31], [32] and [33](Table 5).

Reference： [1]Location in patent: experimental part Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh; Prasad, Ashok K.; Van Der Eycken, Erik; Olsen, Carl E.; Depass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram [European Journal of Medicinal Chemistry, 2011, vol. 46, # 11, p. 5498 - 5511]

15
[ 10538-51-9 ]
[ 111-88-6 ]
S-n-octyl 2',5'-dimethoxythiocinnamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With polyphosphate ester at 20℃;	5.3. Synthesis of the thiocinnamates 29-44 General procedure: A mixture of the commercially available carboxylic acids (1, 2, 4 and 18, 3 mmol), the appropriate commercially available thiol (24-28, 3.1 mmol) and polyphosphate ester (PPE, 2 mL) was stirred at room temperature for 0.5-11 h (refPreviewPlaceHolderScheme 3 and refPreviewPlaceHolderScheme 4). After completion of the reaction, the mixture was treated with saturated aqueous sodium hydrogen carbonate solution (20 mL) and extracted with chloroform (3 × 20 mL). The combined chloroform extract was dried over sodium sulfate and evaporated in a rotary vacuum evaporator. The crude compounds were passed through a silica-gel column, using pure petroleum ether as eluent, the desired compounds were obtained as colorless viscous oils in 92-98% yields. The structures of all the thio esters were unambiguously established on the basis of their spectral (IR, 1H NMR, 13C NMR spectra and HRMS) analysis. The structure of the known esters 38-41 were further confirmed by comparison of their melting points with those reported in the literature [29], [30], [31], [32] and [33](Table 5).

Reference： [1]Location in patent: experimental part Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh; Prasad, Ashok K.; Van Der Eycken, Erik; Olsen, Carl E.; Depass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram [European Journal of Medicinal Chemistry, 2011, vol. 46, # 11, p. 5498 - 5511]

16
[ 10538-51-9 ]
[ 100-53-8 ]
S-benzyl 2',5'-dimethoxythiocinnamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With polyphosphate ester at 20℃;	5.3. Synthesis of the thiocinnamates 29-44 General procedure: A mixture of the commercially available carboxylic acids (1, 2, 4 and 18, 3 mmol), the appropriate commercially available thiol (24-28, 3.1 mmol) and polyphosphate ester (PPE, 2 mL) was stirred at room temperature for 0.5-11 h (refPreviewPlaceHolderScheme 3 and refPreviewPlaceHolderScheme 4). After completion of the reaction, the mixture was treated with saturated aqueous sodium hydrogen carbonate solution (20 mL) and extracted with chloroform (3 × 20 mL). The combined chloroform extract was dried over sodium sulfate and evaporated in a rotary vacuum evaporator. The crude compounds were passed through a silica-gel column, using pure petroleum ether as eluent, the desired compounds were obtained as colorless viscous oils in 92-98% yields. The structures of all the thio esters were unambiguously established on the basis of their spectral (IR, 1H NMR, 13C NMR spectra and HRMS) analysis. The structure of the known esters 38-41 were further confirmed by comparison of their melting points with those reported in the literature [29], [30], [31], [32] and [33](Table 5).

Reference： [1]Location in patent: experimental part Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh; Prasad, Ashok K.; Van Der Eycken, Erik; Olsen, Carl E.; Depass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram [European Journal of Medicinal Chemistry, 2011, vol. 46, # 11, p. 5498 - 5511]

17
[ 10538-51-9 ]
[ 67-63-0 ]
[ 1269597-24-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sulfuric acid Reflux;	5.2.1. General procedure for the synthesis of the cinnamates 10-17 and 20-23 General procedure: A mixture of the commercially available cinnamic acid (4)/substituted cinnamic acids 1-3/dihydrocinnamic acids (18/19, 5 mmol) and the corresponding commercially available alcohols 5-9, i.e. propyl (7)/isopropyl (5)/octyl (8)/phenyl (6)/benzyl alcohol (9) (25 mL) and concentrated sulfuric acid (0.2 mL) was refluxed for 4-5 h (Scheme 1 and Scheme 2). On completion of the reactions as observed from TLC examination, the reaction mixture was neutralized by the addition of 10% aqueous sodium hydrogen carbonate solution (w/v) and then extracted with chloroform (2 × 25 mL), the combined organic layer was separated and dried over anhydrous Na2SO4. The crude product obtained after evaporation of organic solvent was loaded on a small silica gel column and eluted with chloroform to obtain the pure esters in 71-99% yields. The structures of all the cinnamates 10-17 and 20-23 were unambiguously established on the basis of their spectral (IR, 1H NMR, 13C NMR spectra and HRMS) analysis. The structures of the known esters 11, 16 and 17 were further confirmed by comparison of their melting points with those reported in the literature [27] and [28] (Table 5).

Reference： [1]Location in patent: experimental part Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh; Prasad, Ashok K.; Van Der Eycken, Erik; Olsen, Carl E.; Depass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram [European Journal of Medicinal Chemistry, 2011, vol. 46, # 11, p. 5498 - 5511]

18
[ 10538-51-9 ]
[ 75-08-1 ]
S-ethyl 2',5'-dimethoxythiocinnamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With polyphosphate ester at 20℃;	5.3. Synthesis of the thiocinnamates 29-44 General procedure: A mixture of the commercially available carboxylic acids (1, 2, 4 and 18, 3 mmol), the appropriate commercially available thiol (24-28, 3.1 mmol) and polyphosphate ester (PPE, 2 mL) was stirred at room temperature for 0.5-11 h (refPreviewPlaceHolderScheme 3 and refPreviewPlaceHolderScheme 4). After completion of the reaction, the mixture was treated with saturated aqueous sodium hydrogen carbonate solution (20 mL) and extracted with chloroform (3 × 20 mL). The combined chloroform extract was dried over sodium sulfate and evaporated in a rotary vacuum evaporator. The crude compounds were passed through a silica-gel column, using pure petroleum ether as eluent, the desired compounds were obtained as colorless viscous oils in 92-98% yields. The structures of all the thio esters were unambiguously established on the basis of their spectral (IR, 1H NMR, 13C NMR spectra and HRMS) analysis. The structure of the known esters 38-41 were further confirmed by comparison of their melting points with those reported in the literature [29], [30], [31], [32] and [33](Table 5).

Reference： [1]Location in patent: experimental part Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh; Prasad, Ashok K.; Van Der Eycken, Erik; Olsen, Carl E.; Depass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram [European Journal of Medicinal Chemistry, 2011, vol. 46, # 11, p. 5498 - 5511]

19
[ 10538-51-9 ]
[ 108-95-2 ]
[ 1012522-76-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sulfuric acid Reflux;	5.2.1. General procedure for the synthesis of the cinnamates 10-17 and 20-23 General procedure: A mixture of the commercially available cinnamic acid (4)/substituted cinnamic acids 1-3/dihydrocinnamic acids (18/19, 5 mmol) and the corresponding commercially available alcohols 5-9, i.e. propyl (7)/isopropyl (5)/octyl (8)/phenyl (6)/benzyl alcohol (9) (25 mL) and concentrated sulfuric acid (0.2 mL) was refluxed for 4-5 h (Scheme 1 and Scheme 2). On completion of the reactions as observed from TLC examination, the reaction mixture was neutralized by the addition of 10% aqueous sodium hydrogen carbonate solution (w/v) and then extracted with chloroform (2 × 25 mL), the combined organic layer was separated and dried over anhydrous Na2SO4. The crude product obtained after evaporation of organic solvent was loaded on a small silica gel column and eluted with chloroform to obtain the pure esters in 71-99% yields. The structures of all the cinnamates 10-17 and 20-23 were unambiguously established on the basis of their spectral (IR, 1H NMR, 13C NMR spectra and HRMS) analysis. The structures of the known esters 11, 16 and 17 were further confirmed by comparison of their melting points with those reported in the literature [27] and [28] (Table 5).

Reference： [1]Location in patent: experimental part Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh; Prasad, Ashok K.; Van Der Eycken, Erik; Olsen, Carl E.; Depass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram [European Journal of Medicinal Chemistry, 2011, vol. 46, # 11, p. 5498 - 5511]

20
[ 10538-51-9 ]
[ 1357258-99-1 ]
(2E)-(3aR,5aR,9bS)-2,3,3a,4,5,5a,6,7,8,9b-decahydro-3a-hydroxy-3,5a,9-trimethyl-2-oxonaphtho[1,2-b]furan-8-yl 3-(2,5-dimethoxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%	With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h;	8 Example 8Synthesis of (2E)-(3aR.5aR.9bSV2.3.3a.4.5.5a.6<7.8.9b-decahvdro-3a-hvdroxv-3.5a,9- trimethyl-2-oxonaphtho[ 1 ,2-b]furan-8-yl 3 -(2, 5 -dimethoxyphenyDacrylate [compound- 16. (18)1: A solution of (3aR,5aR,9bS)-3,3a,4,5,5a,6,7,8-octahydro-3a,8-dihydroxy-5a,9- dimethyl-3-methylenenaphtho[l,2-b]furan-2(9bH)-one (compound-10; 300 mg, 0.001 13 mol), 2, 5-dimethoxy cinnamic acid (280 mg, 0.013 mol), 6mL of methylene dichloride (MDC), 50 mg of dimethylaminopyridine (DMAP) was taken in a RB flask and treated slowly with a solution of 351 mg of dicyclohexylcarbodiimide (DCC) (0.0017 mol) dissolved in 4mL of MDC under stirring at 0°C. The RM was then allowed to RT and continued the stirring for 2h. The RM was then poured into ice-cold water and the mixture extracted with EtOAc. The organic layer was washed with brine, dried over Na2S04 and concentrated under vacuum. The residue (600 mg) was subjected to column chromatography on silica column using acetone/hexane mixtures to obtain 120 mg of compound- 16 (18, 24%) in the fraction eluted with 25% of acetone/hexane.Compound-16: NMR (CDC13> 400MHz): δ 7.91 (1H, d, J = 16.0Hz), 7.44 (1H, d, J = 8.4Hz), 6.50 (1H, dd, J = 8.4, 2.4 Hz), 6.46 (1H, d, J = 16.0 Hz), 6.48 (1H, d, J = 2.0Hz), 5.34 (1H, d, J = 4.0Hz), 3.88 (3H, s), 3.84 (3H, s), 2.52 (1H, q, J = 7.6Hz), 2.05 (2H, m), 1.848(3H, s), 1.84 (2H, m), 1.68 (2H, m), 1.47 (1H, m), 1.138(1H, m), 1.34 (3H, d, J = 7.6Hz), 1.23 (1H, m), 1.10 (3H, s); LC/MS: 479.3 (M+Na)+ positive ion mode, 455 (M- H) 491 (M+2H20-H)" negative ion mode.

Reference： [1]Current Patent Assignee: LAILA GROUP PVT LTD - WO2012/14216, 2012, A1 Location in patent: Page/Page column 37

21
[ 10538-51-9 ]
[ 1380394-76-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	With tert.-butylhydroperoxide; copper(ll) sulfate pentahydrate; Langlois reagent In dichloromethane; water at 50℃; for 8h; stereospecific reaction;

Reference： [1]Li, Zejiang; Cui, Zili; Liu, Zhong-Quan [Organic Letters, 2013, vol. 15, # 2, p. 406 - 409]

22
[ 10538-51-9 ]
[ 1418317-51-7 ]

Yield	Reaction Conditions	Operation in experiment
40%	With tert.-butylhydroperoxide; ferrous(II) sulfate heptahydrate; bis(((difluoromethyl)sulfinyl)oxy)zinc In dichloromethane; water at 50℃; for 22h; stereospecific reaction;

Reference： [1]Li, Zejiang; Cui, Zili; Liu, Zhong-Quan [Organic Letters, 2013, vol. 15, # 2, p. 406 - 409]

23
[ 1779-81-3 ]
[ 10538-51-9 ]
[ 737822-46-7 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 12h; Inert atmosphere;	II. Experimental Procedure General procedure: (E)-3-(4-ethylphenyl)acrylic acid (100 mg, 0.567 mmol), 3-((ethylimino)methyleneamino)-N,N-dimethylpropan-1-aminium chloride (163 mg, 0. 851 mmol), and N,N-dimethylpyridin-4-amine (13 mg, 0.19 mmol) were dissolved in dichloromethane (10 mL). N-ethyl-N-isopropylpropan-2-amine (161 mg, 1.248 mmol) was added followed by 4,5-dihydrothiazol-2-amine (64 mg, 0.624 mmol). The reaction mixture was stirred for 12 hours at room temperature. The reaction was concentrated under vacuum. Purification by column chromatography provided (E)-N-(4,5-dihydrothiazol-2-yl)-3-(4-ethylphenyl)acrylamide as a white powder (58 mg, 40% yield).

Reference： [1]Germain, Andrew R.; Carmody, Leigh C.; Nag, Partha P.; Morgan, Barbara; Verplank, Lynn; Fernandez, Cristina; Donckele, Etienne; Feng, Yuxiong; Perez, Jose R.; Dandapani, Sivaraman; Palmer, Michelle; Lander, Eric S.; Gupta, Piyush B.; Schreiber, Stuart L.; Munoz, Benito [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 6, p. 1834 - 1838]

24
[ 10538-51-9 ]
[ 60-12-8 ]
3-(2,5-dimethoxyphenyl)acrylic acid phenethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 2-phenylethanol With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 2,5-dimethoxycinnamic acid In dichloromethane at 20℃;

Reference： [1]Wang, Yan-Hui; Li, Qu-Sheng; Wang, Peng-Long; Xu, Kuo; Cheng, Ya-Tao; Xu, Xin; Li, Qiang; Zhang, Yu-Zhong; Lei, Hai-Min [Asian Journal of Chemistry, 2014, vol. 26, # 9, p. 2686 - 2690]

25
[ 10538-51-9 ]
[ 52428-09-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: palladium 10% on activated carbon; hydrogen / ethyl acetate / 2068.65 Torr 2.1: thionyl chloride; N,N-dimethyl-formamide / 5 h / Reflux 2.2: 0.83 h / -5 °C
	Multi-step reaction with 3 steps 1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 48 h / 23 °C 2: thionyl chloride; N,N-dimethyl-formamide / 2 h / 23 °C / Inert atmosphere 3: aluminum (III) chloride / dichloromethane / 0.17 h / 0 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; hydrogen / 760.05 Torr 2: phosphorus pentoxide; methanesulfonic acid / dichloromethane / 19 h / 20 °C

Reference： [1]Mejlsoe, Soren L.; Christensen, Jorn B. [Journal of Heterocyclic Chemistry, 2014, vol. 51, # 4, p. 1051 - 1057]
[2]Kim, Yun Yeong; Pyun, Yu Mi; Jeon, Bo Keun; Lee, Duck-Hyung [Bulletin of the Korean Chemical Society, 2018, vol. 39, # 5, p. 597 - 598]
[3]Kotha, Sambasivarao; Cheekatla, Subba Rao; Mandal, Binita [European Journal of Organic Chemistry, 2017, vol. 2017, # 29, p. 4277 - 4282]

26
[ 10538-51-9 ]
[ 118-93-4 ]
C₁₉H₁₈O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; trichlorophosphate at 20℃; Cooling with ice;	3.3. General Procedure for the Synthesis of II General procedure: Phosphoryl chloride (POCl3; 20 mmol) was added slowly to a 100 mL SNRB flask containing a mixture of I (5.5 mmol) and the appropriate 2'-hydroxyacetophenone (5 mmol) in pyridine (30 mL). The flask was placed in an ice bath and the reaction mixture was left overnight, with constant stirring at room temperature. The reaction mixture was then poured into 100 mL cold, dilute HCl in a 250 mL EF, followed by extraction with ethyl acetate (EA). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product obtained was further purified by open column chromatography.

Reference： [1]Leong, Sze Wei; Mohd Faudzi, Siti Munirah; Abas, Faridah; Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Wai, Lam Kok; Abdul Bahari, Mohd Nazri; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H. [Molecules, 2014, vol. 19, # 10, p. 16058 - 16081]

27
[ 1450-74-4 ]
[ 10538-51-9 ]
C₁₉H₁₇ClO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; trichlorophosphate at 20℃; Cooling with ice;	3.3. General Procedure for the Synthesis of II General procedure: Phosphoryl chloride (POCl3; 20 mmol) was added slowly to a 100 mL SNRB flask containing a mixture of I (5.5 mmol) and the appropriate 2'-hydroxyacetophenone (5 mmol) in pyridine (30 mL). The flask was placed in an ice bath and the reaction mixture was left overnight, with constant stirring at room temperature. The reaction mixture was then poured into 100 mL cold, dilute HCl in a 250 mL EF, followed by extraction with ethyl acetate (EA). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product obtained was further purified by open column chromatography.

Reference： [1]Leong, Sze Wei; Mohd Faudzi, Siti Munirah; Abas, Faridah; Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Wai, Lam Kok; Abdul Bahari, Mohd Nazri; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H. [Molecules, 2014, vol. 19, # 10, p. 16058 - 16081]

28
[ 552-41-0 ]
[ 10538-51-9 ]
C₂₀H₂₀O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; trichlorophosphate at 20℃; Cooling with ice;	3.3. General Procedure for the Synthesis of II General procedure: Phosphoryl chloride (POCl3; 20 mmol) was added slowly to a 100 mL SNRB flask containing a mixture of I (5.5 mmol) and the appropriate 2'-hydroxyacetophenone (5 mmol) in pyridine (30 mL). The flask was placed in an ice bath and the reaction mixture was left overnight, with constant stirring at room temperature. The reaction mixture was then poured into 100 mL cold, dilute HCl in a 250 mL EF, followed by extraction with ethyl acetate (EA). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product obtained was further purified by open column chromatography.

Reference： [1]Leong, Sze Wei; Mohd Faudzi, Siti Munirah; Abas, Faridah; Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Wai, Lam Kok; Abdul Bahari, Mohd Nazri; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H. [Molecules, 2014, vol. 19, # 10, p. 16058 - 16081]

29
[ 705-15-7 ]
[ 10538-51-9 ]
C₂₀H₂₀O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; trichlorophosphate at 20℃; Cooling with ice;	3.3. General Procedure for the Synthesis of II General procedure: Phosphoryl chloride (POCl3; 20 mmol) was added slowly to a 100 mL SNRB flask containing a mixture of I (5.5 mmol) and the appropriate 2'-hydroxyacetophenone (5 mmol) in pyridine (30 mL). The flask was placed in an ice bath and the reaction mixture was left overnight, with constant stirring at room temperature. The reaction mixture was then poured into 100 mL cold, dilute HCl in a 250 mL EF, followed by extraction with ethyl acetate (EA). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product obtained was further purified by open column chromatography.

Reference： [1]Leong, Sze Wei; Mohd Faudzi, Siti Munirah; Abas, Faridah; Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Wai, Lam Kok; Abdul Bahari, Mohd Nazri; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H. [Molecules, 2014, vol. 19, # 10, p. 16058 - 16081]

30
[ 10538-51-9 ]
[ 3321-92-4 ]
C₁₉H₁₆Cl₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; trichlorophosphate; at 20℃;Cooling with ice;	General procedure: Phosphoryl chloride (POCl3; 20 mmol) was added slowly to a 100 mL SNRB flask containing a mixture of I (5.5 mmol) and the appropriate 2'-hydroxyacetophenone (5 mmol) in pyridine (30 mL). The flask was placed in an ice bath and the reaction mixture was left overnight, with constant stirring at room temperature. The reaction mixture was then poured into 100 mL cold, dilute HCl in a 250 mL EF, followed by extraction with ethyl acetate (EA). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product obtained was further purified by open column chromatography.

Reference： [1]Molecules,2014,vol. 19,p. 16058 - 16081

31
[ 10538-51-9 ]
aminohexane geldanamycin [ No CAS ]
17-(6-(2,5-dimethoxycinnamamido)hexylamino)-17-demethoxygeldanamycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 24h;	4.4. General procedure for preparation of 7a-g and 7h1-32 General procedure: Compound 6 was dissolved in 10 mL of dimethyl formamide and treated with EDC*HCl (1.2 equiv.), NHS (1.2 equiv.) and substitutional carboxylic acid (1.2 equiv.). The reaction mixture was stirred overnight at room temperature. TLC was used to monitor the progress of the reaction. After the reaction complete, the mixture was poured into 40 mL of water and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was washed by brine (3 x 30 mL), dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The residue was purified by flash column chromatography (silica gel, ethyl acetate/petroleum ether 1:1) to afford 7a as a purple solid.

Reference： [1]Li, Zhenyu; Jia, Lejiao; Wang, Jifeng; Wu, Xingkang; Hao, Huilin; Wu, Yunfei; Xu, Hongjiao; Wang, Zhen; Shi, Guowei; Lu, Chunhua; Shen, Yuemao [European Journal of Medicinal Chemistry, 2014, vol. 87, p. 346 - 363]

32
[ 10538-51-9 ]
[ 79074-45-6 ]
(E)-(3,5,6-trimethylpyrazin-2-yl)methyl 3-(2,5-dimethoxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 1.5h; Inert atmosphere;

Reference： [1]Xu, Bing; Gong, Yan; Xu, Xin; Zhang, Chenze; Zhang, Yuzhong; Chu, Fuhao; Liu, Hongbing; Wang, Penglong; Lei, Haimin [MedChemComm, 2015, vol. 6, # 5, p. 806 - 809]

33
[ 10538-51-9 ]
[ 866751-49-7 ]
C₁₉H₂₃N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.5%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h;	11 Example 11: preparaton of L8 (Compound No. 8) Round-bottomed flask were added sequentially 274.56mg (1.32mmol) 2,5-dimethoxy-cinnamic acid, 4.30 mL (1.33mmol) TMP-NH2The CH2Cl2Solution, 253mg (1.32mmol) EDCI, 528μL (3.97mmol) triethylamine; 20mL of methylene chloride was added, the reaction was stirred at room temperature 12 h.TLC [V (petroleum ether) :V (acetone) = 2] Detection reaction is essentially complete, the reaction was successively washed with water (2 × 20 mL) and saturated brine (20 mL) wash, dried over anhydrous sodium sulfate, filtered, and reduced pressure evaporated to dryness.The residue was separated by silica gel column white solid, yield: 88.5%,

Reference： [1]Current Patent Assignee: Lei, Haimin; Wang, Penglong; Li, Guoliang; Liu, Wei; Zhang, Yuzhong - CN105596337, 2016, A Location in patent: Paragraph 0064; 0065; 0066

34
[ 10538-51-9 ]
decursinol [ No CAS ]
[ 1001129-79-8 ]

Yield	Reaction Conditions	Operation in experiment
38.7%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	General procedure for the synthesis of cinnamoyl-, haro-cinnamoyl-, NO2-cinnamoyl- and (OCH3)ncinnamoyl-decursin derivatives (5a-e, 6a-i) General procedure: The mixture of cinnamic acid (1.2 equiv), EDC (2 equiv) and 4-DMAP (0.4 equiv) was dissolved inanhydrous dichloromethane. After (+)-Decursinol (1 equiv) was added, the reaction mixture stirred to roomtemperature for 5-12 hours. The completion of reaction was juged by TLC. When a spot of (+)-decursinolwas disappeared on TLC, the reaction was finished. The mixture was concentrated in vacuo and the residuewas purified by flash silica gel column chromatography using EtOAc/Hexane system as eluent.

Reference： [1]Lee, Jee-Hyun; Kim, Min-Ah; Park, Seoyoung; Cho, Soo-Hyun; Yun, Eunju; O, Yu-Seok; Kim, Jiseon; Goo, Ja-Il; Yun, Mi-Young; Choi, Yongseok; Oh, Sangtaek; Song, Gyu-Yong [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 15, p. 3529 - 3532]

35
[ 10538-51-9 ]
[ 133745-75-2 ]
(E)-N-(2,5-dimethoxystyryl)-N-(phenylsulfonyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine In acetonitrile at 70℃; for 24h; Sealed tube; Inert atmosphere; regioselective reaction;

Reference： [1]Fang, Zhongxue; Feng, Yu; Dong, Hai; Li, Dashan; Tang, Tiandi [Chemical Communications, 2016, vol. 52, # 74, p. 11120 - 11123]

36
[ 10538-51-9 ]
bis(2,5-dimethoxycinnamic) anhydride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: 2,5-dimethoxycinnamic acid With Bromotrichloromethane; triphenylphosphine In dichloromethane for 5h; Reflux; Stage #2: With triethylamine In dichloromethane for 8h; Reflux;	b.8 General procedure for the preparation of carboxylic acidanhydrides General procedure: To a solution of triphenylphosphine (910 mg,3.47 mmol) in dry dichloromethane (10 mL) bromotrichloromethane(710 mg, 3.58 mmol) was added, and theresulting mixture was stirred at a rate for 30 min to give areddish-brownish solution. Thereafter, cinnamic acid (4a,451 mg, 3.05 mmol) was added, and the resulting mixturewas held at reflux for 5 h. Thereafter, cinnamic acid(451 mg, 3.05 mmol) and subsequently triethylamine(310 mg, 3.05 mmol) were added, and the reaction mixturewas held at reflux for 8 h. Then, the cooled solution wasconcentrated in vacuo, and the concentrate was subjectedto rapid column chromatography on a silica gel [CH2Cl2-hexane 2:1] to give cinnamic anhydride (9a, 605 mg, 71%)as colorless crystals;

Reference： [1]Al-Azani, Mariam; al-Sulaibi, Mazen; al Soom, Nuha; Al Jasem, Yosef; Bugenhagen, Bernhard; Al Hindawi, Bassam; Thiemann, Thies [Comptes Rendus Chimie, 2016, vol. 19, # 8, p. 921 - 932]

37
[ 10538-51-9 ]
[ 106-20-7 ]
N,N-bis(2-ethylhexyl) 3-(1,4-dimethoxyphen-2-yl)propenoic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 2,5-dimethoxycinnamic acid With Bromotrichloromethane; triphenylphosphine In dichloromethane for 0.75h; Reflux; Stage #2: 2-ethyl-N-(2-ethylhexyl)-1-hexanamine In dichloromethane for 14h; Reflux;	2.1 N,N-Bis(2-ethylhexyl) 3-(1,4-dimethoxyphen-2-yl)propenoic acid amide To a solution of PPh3 (980 mg, 3.74 mmol) in dry CH2Cl2(12 mL) BrCCl3 (1.50 g, 7.66 mmol)was added. The resultingmixture was stirred at rt for 30 min, during which it turnedreddish-brown. Thereafter, 2,5-dimethoxycinnamic acid(4c, 700 mg, 3.37 mmol) was added, and the mixture washeated under reflux for 45 min. Thereafter, di(2-ethylhexyl)amine (1.62 g, 6.71 mmol) was added dropwise via a syringe,where the ensuing reaction is exothermic. The reactionmixture was stirred at reflux for 14 h. Then, thecooled mixture was concentrated in vacuo, and the residuewas subjected directly to column chromatography on asilica gel to give 5f (875 mg, 2.03 mmol, 60%) as a colorlessoil; nmax neat/cm1) 2961, 2877, 1660, 1622, 1506, 1489,1047, 772; dH (400 MHz, CDCl3) 1.00 (16H, m),1.48 (20H, m),1.69e1.79 (2H, m), 3.28e3.43 (4H, m), 3.77 (3H, s, OCH3),3.81 (3H, s, OCH3), 6.82 (1H, d, 3J 8.8 Hz), 6.84 (1H, d,3J 8.8 Hz), 7.00 (1H, s), 7.02 (1H, d, 3J 15.6 Hz), 7.86 (1H,d, 3J 15.6 Hz); dC (67.8 MHz, CDCl3, DEPT) 10.7 (CH3), 10.8(CH3), 14.0 (CH3), 14.1 (CH3), 23.1 (CH2, 2C), 23.7 (CH2), 24.0(CH2), 28.7 (CH2), 28.8 (CH2), 30.5 (CH2), 30.7 (CH2), 37.6 (CH), 40.0 (CH), 50.7 (CH2), 52.0 (CH2), 55.7 (OCH3), 56.0(CH3), 112.3 (CH), 114.4 (CH), 115.4 (CH), 119.6 (CH), 125.2(Cquat), 137.5 (CH), 152.8 (Cquat), 153.4 (Cquat), 167.3 (Cquat,CO).

Reference： [1]Al-Azani, Mariam; al-Sulaibi, Mazen; al Soom, Nuha; Al Jasem, Yosef; Bugenhagen, Bernhard; Al Hindawi, Bassam; Thiemann, Thies [Comptes Rendus Chimie, 2016, vol. 19, # 8, p. 921 - 932]

38
[ 10538-51-9 ]
[ 704902-18-1 ]
C₁₇H₂₄N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 20℃; for 24h;	Preparation of library I and II General procedure: In each 200 μL well of a microtiter plate, a mixture of diisopropyl ethylamine (5.0 μL, 180.0mM solution in DMSO), HBTU (5 μL, 90mM solutionin DMSO), a carboxylic acid (10.0 μL, 30.0mM solution in DMSO) and a scaffold (compound 1and 2 ) (10.0μL, 30.0mM solution in DMSO) was shaken at rt for 24 h and analyzed by ESI-MS (or TLC) to verify the presence of the desired product. Each reaction mixture was diluted with H2O and transferred to another 96-well microtiter plate to make a 20 mM solution per each desired molecule (based on 100% conversion of amine) for the enzymatic assay directly without further purification.

Reference： [1]Cheng, Wei-Chieh; Wang, Jen-Hon; Yun, Wen-Yi; Li, Huang-Yi; Hu, Jia-Ming [European Journal of Medicinal Chemistry, 2017, vol. 126, p. 1 - 6]

39
[ 10538-51-9 ]
(2S,3R,4S,5R)-2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol [ No CAS ]
C₁₇H₂₄N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 20℃; for 24h;	Preparation of library I and II General procedure: In each 200 μL well of a microtiter plate, a mixture of diisopropyl ethylamine (5.0 μL, 180.0mM solution in DMSO), HBTU (5 μL, 90mM solutionin DMSO), a carboxylic acid (10.0 μL, 30.0mM solution in DMSO) and a scaffold (compound 1and 2 ) (10.0μL, 30.0mM solution in DMSO) was shaken at rt for 24 h and analyzed by ESI-MS (or TLC) to verify the presence of the desired product. Each reaction mixture was diluted with H2O and transferred to another 96-well microtiter plate to make a 20 mM solution per each desired molecule (based on 100% conversion of amine) for the enzymatic assay directly without further purification.

Reference： [1]Cheng, Wei-Chieh; Wang, Jen-Hon; Yun, Wen-Yi; Li, Huang-Yi; Hu, Jia-Ming [European Journal of Medicinal Chemistry, 2017, vol. 126, p. 1 - 6]

40
[ 10538-51-9 ]
[ 471-53-4 ]
(2,5-dimethoxy)cinnamoyl-3β-hydroxy-11-οxοοlean-12-en-30-οic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57.1%	Stage #1: 2,5-dimethoxycinnamic acid; enoxolone With dmap In dichloromethane at 4℃; for 0.166667h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 4 - 20℃; for 24.5h;	7 (2,5-dimethoxy)cinnamoyl-3β-Hydroxy-11-oxoolean-12-en-30-oic acid (7a) Place 6.0mmol of 2,5-dimethoxycinnamic acid and 0.6mmol of DMAP in a 100ml round bottom flask, add 50ml of methylenechloride and stir for 10-20min. After fully dissolve, add 3.0mmol of glycyrrhetinic acid and stir for 10min. After bathing at 4°C,EDCI dichloromethane solution was slowly added dropwise. After the addition was continued for about 30 minutes at 4°C, the reaction was carried out at room temperature for 24 hours. After completion of the reaction, the solution was washed with saturated sodium bicarbonate solution and saturated brine twice, dried over anhydrous sodium sulfate, and the solvent was recovered. The resulting solid was separated by column chromatography (dichloromethane:methanol=200:1) to give whitesolids. 1.132 g of powder with a yield of 57.1%.

Reference： [1]Current Patent Assignee: Lei Haimin; Wang Penglong; Yan Mengmeng; Guo Wenbo - CN107474097, 2017, A Location in patent: Paragraph 0074; 0075; 0076

41
[ 10538-51-9 ]
[ 254454-54-1 ]
tert-butyl (E)-3-(2,5-dimethoxystyryl)azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With 1,1'-bis-(diphenylphosphino)ferrocene; bis(acetylacetonato)palladium(II); N-Methyldicyclohexylamine In N,N-dimethyl acetamide at 90℃; for 8h; Inert atmosphere; stereoselective reaction;

Reference： [1]Han, Shuaijun; Ren, Xiaoxiao; Wu, Qingsong; Liang, Apeng; Li, Jingya; Zou, Dapeng; Wu, Yangjie; Wu, Yusheng [Advanced Synthesis and Catalysis, 2018, vol. 360, # 12, p. 2308 - 2312]

42
[ 10538-51-9 ]
[ 14568-68-4 ]

Yield	Reaction Conditions	Operation in experiment
	With ferulic acid decarboxylase from Saccharomyces cerevisae In aq. phosphate buffer; dimethyl sulfoxide at 30℃; for 18h; Enzymatic reaction;

Reference： [1]Aleku, Godwin A.; Prause, Christoph; Bradshaw-Allen, Ruth T.; Plasch, Katharina; Glueck, Silvia M.; Bailey, Samuel S.; Payne, Karl A. P.; Parker, David A.; Faber, Kurt; Leys, David [ChemCatChem, 2018, vol. 10, # 17, p. 3736 - 3745]

43
[ 10538-51-9 ]
C₂₄H₃₈N₂O₃ [ No CAS ]
C₃₅H₄₈N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31 mg	Stage #1: 2,5-dimethoxycinnamic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 0.5h; Stage #2: C₂₄H₃₈N₂O₃ In dichloromethane at 20℃;	General procedure: To a solution of corresponding cinnamic acid (1.1 equiv) in dry CH2Cl2 (3mL) were added 2-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (29mg, 0.15mmol) and N,N-diisopropylethylamine (DIPEA) (29mg, 0.225mmol) at room temperature. After 0.5h, the above yellow oil (77mg) was added, and the reaction mixture was stirred at room temperature for 16h. The volatiles were removed under reduced pressure, and the residue was partitioned between EtOAc and H2O. The EtOAc layer was dried over MgSO4 and condensed to afford a crude residue. The residue was purified by silica gel column chromatography with petroleum ether/acetone (2:1) to produce the desired products 5a-5o, respectively.

Reference： [1]Ge, Yong-Xi; Wang, Yan-Hong; Zhang, Juan; Yu, Zhi-Pu; Mu, Xin; Song, Jia-Li; Wang, Yin-Yin; Yang, Feifei; Meng, Ning; Jiang, Cheng-Shi; Zhang, Hua [Steroids, 2019, vol. 152]

44
[ 288-32-4 ]
[ 10538-51-9 ]
C₁₄H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 2,5-dimethoxycinnamic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 1H-imidazole In tetrahydrofuran at 20℃; Inert atmosphere;	3 (Production Example 1) Synthesis of cinnamic acid amide-type thermal base gen General procedure: In a 300 mL 2 neck flask,trans-2-methoxycinnamic acid (2.17 g, 12.2 mmol),1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride(2.81 g, 14.6 mmol) was added, and the system was replaced with N2, and then dry THF (80 mL) was added.After stirring at room temperature for 30 minutes, imidazole (1.00 g, 14.6 mmol) was added, and the mixture was stirred at room temperature overnight.After distilling off the solvent from the obtained reaction solution under reduced pressure,The mixture was extracted with chloroform, and the obtained organic layer was further diluted with dil. HCl,NaHCO3aq. And washed.After the organic layer was dried over MgSO4, the solvent was distilled off under reduced pressure to obtain a crude product.Purified by silica gel column chromatography (chloroform / methanol, 100: 1),A thermal base generator (1) (1.42 g, 51% yield) represented by the following chemical formula was obtained.

Reference： [1]Current Patent Assignee: TAIYO HOLDINGS CO., LTD. - JP2019/189539, 2019, A Location in patent: Paragraph 0046-0051

45
[ 79-10-7 ]
[ 150-78-7 ]
[ 10538-51-9 ]

Yield	Reaction Conditions	Operation in experiment
51%	With dipotassium peroxodisulfate; palladium diacetate In 1,4-dioxane; acetic acid at 80℃; for 24h;	General procedure for the synthesis of compounds General procedure: Typical coupling procedure: Pd(OAc)2 (22 mg, 5 mol%), K2S2O8 (0.81 g 3 mmol), alkene (2 mmol), arene (15 mmol, 7.5 equiv.), acetic acid (8 mL) and cosolvent (2 mL) were placed in a 20 mL scintillation vial containing a magnetic stirrer bar. The flask was sealed with a Teflon-lined crimped cap, and the reaction solution was stirred vigorously at 80 °C 24 h (unless otherwise specified). The reaction solution was cooled to room temperature, CH2Cl2 added, filtered and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel using cyclohexane/ethyl acetate to afford the desired product.

Reference： [1]Jones, Roderick C. [Tetrahedron Letters, 2020, vol. 61, # 6]

46
[ 10538-51-9 ]
[ 104-94-9 ]
(E)-3-(2,5-dimethoxyphenyl)-N-(4-methoxyphenyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: 2,5-dimethoxycinnamic acid; 4-methoxy-aniline With thionyl chloride for 3h; Reflux; Stage #2: With triethylamine In dichloromethane at 20℃;

Reference： [1]Bayrak, Cetin; Menzek, Abdullah; Sevim, Melike [Journal of Organometallic Chemistry, 2022, vol. 958]

47
[ 10538-51-9 ]
5-((1H-indol-3-yl)methyl)-3-(piperazin-1-ylmethyl)-1,2,4-oxadiazole [ No CAS ]
(E)-1-(4-((5-((1H-indol-3-yl)methyl)-1,2,4-oxadiazol-3-yl)methyl)piperazin-1-yl)-3-(2,5-dimethoxyphenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	4.1.5. General procedure for the preparation of compounds D-1 - D-28 General procedure: Method B for the synthesis of D-10 - D-28: compound 5 (50 mg,0.168 mmol, 1 equiv.) was dissolved in 5 mL CH2Cl2 in a vial. EDCI (1.5equiv.) and HOBT (1.0 equiv.) were added to the reaction mixture. Aseries of corresponding benzoic acids or cinnamic acids (1.1 equiv.) andEt3N (3 equiv.) were added. The reaction mixture was stirred overnightat room temperature. Upon completion of the reaction, water (10 mL)was added and the product was extracted with CH2Cl2 (3 × 10 mL). Thecombined organic layers were dried using anhydrous MgSO4, thenconcentrated under vacuum, and the residues were purified by flashcolumn chromatography using petroleum ether:acetone = 3:1 as aneluent to give the target compounds.
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	4.1.5. General procedure for the preparation of compounds D-1 - D-28 General procedure: Method B for the synthesis of D-10 - D-28: compound 5 (50 mg,0.168 mmol, 1 equiv.) was dissolved in 5 mL CH2Cl2 in a vial. EDCI (1.5equiv.) and HOBT (1.0 equiv.) were added to the reaction mixture. Aseries of corresponding benzoic acids or cinnamic acids (1.1 equiv.) andEt3N (3 equiv.) were added. The reaction mixture was stirred overnightat room temperature. Upon completion of the reaction, water (10 mL)was added and the product was extracted with CH2Cl2 (3 × 10 mL). Thecombined organic layers were dried using anhydrous MgSO4, thenconcentrated under vacuum, and the residues were purified by flashcolumn chromatography using petroleum ether:acetone = 3:1 as aneluent to give the target compounds.

Reference： [1]Xie, Hong-Xu; Wang, Yan-Hong; Zhang, Jin-He; Zhang, Juan; Zhong, Ying-Nan; Ge, Yong-Xi; Cheng, Zhi-Qiang; Jiang, Cheng-Shi; Meng, Ning [Bioorganic Chemistry, 2022, vol. 120]
[2]Xie, Hong-Xu; Wang, Yan-Hong; Zhang, Jin-He; Zhang, Juan; Zhong, Ying-Nan; Ge, Yong-Xi; Cheng, Zhi-Qiang; Jiang, Cheng-Shi; Meng, Ning [Bioorganic Chemistry, 2022, vol. 120]

48
[ 10538-51-9 ]
10-fluoro-7-ethylcamptothecin [ No CAS ]
7-ethyl-10-fluoro-20-O-(2,5-dimethoxyphenyl)acrylatecamptothecin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With 4-dimethylaminopyridine; diisopropyl-carbodiimide In dichloromethane at 0℃; for 0.5h;	2.1.2. General procedure for the synthesis of compound XJS-1 ~ XJS-18 General procedure: Compound 10 (2.0 mmol) and the substituted cinnamic acids CA-1~ CA-18 (2.4 mmol) in anhydrous CH2Cl2 (10 mL) was added withDMAP (2.4 mmol) and DIPC (4.8 mmol) at 0 C. After stirring for 30 min,the reaction mixture was allowed to warm to room temperature. Afterthe reaction was completed, as monitored by TLC, the reaction mixturewas washed with 10% NaHCO3 (2 × 20 mL), and 1 N HCl (2 × 20 mL).The combined organic layers, dried over Na2SO4, filtered, and concentratedin vacuo. The crude residue was purified by chromatography onsilica gel with DCM/MeOH to give compounds XJS-1 ~ XJS-18.
86%	With 4-dimethylaminopyridine; diisopropyl-carbodiimide In dichloromethane at 0℃; for 0.5h;	2.1.2. General procedure for the synthesis of compound XJS-1 ~ XJS-18 General procedure: Compound 10 (2.0 mmol) and the substituted cinnamic acids CA-1~ CA-18 (2.4 mmol) in anhydrous CH2Cl2 (10 mL) was added withDMAP (2.4 mmol) and DIPC (4.8 mmol) at 0 C. After stirring for 30 min,the reaction mixture was allowed to warm to room temperature. Afterthe reaction was completed, as monitored by TLC, the reaction mixturewas washed with 10% NaHCO3 (2 × 20 mL), and 1 N HCl (2 × 20 mL).The combined organic layers, dried over Na2SO4, filtered, and concentratedin vacuo. The crude residue was purified by chromatography onsilica gel with DCM/MeOH to give compounds XJS-1 ~ XJS-18.

Reference： [1]Bai, Yin-Peng; Deng, Nan; Li, Lei; Liu, Ying-Qian; Luo, Xiong-Fei; Ma, Yue; Xu, Chuan-Rui; Yang, Cheng-Jie; Zhang, Bao-Qi; Zhang, Mi; Zhang, Zhi-Jun; Zhou, Yong [Biochemical Pharmacology, 2022, vol. 200]
[2]Bai, Yin-Peng; Deng, Nan; Li, Lei; Liu, Ying-Qian; Luo, Xiong-Fei; Ma, Yue; Xu, Chuan-Rui; Yang, Cheng-Jie; Zhang, Bao-Qi; Zhang, Mi; Zhang, Zhi-Jun; Zhou, Yong [Biochemical Pharmacology, 2022, vol. 200]

49
[ 10538-51-9 ]
4-(2,5-dimethoxyphenyl)-1-phenylpyrrolidin-2-one [ No CAS ]
(R)-4-(2,5-dimethoxyphenyl)-1-phenylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride / dichloromethane / 0.5 h / 20 °C / Inert atmosphere; Reflux; Schlenk technique 2: (4bR,11aS)-4b,11a-dihydro-12H-benzo[d]indeno[1',2':4,5]imidazo[2,1-b]thiazole; 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium salt; tetra-n-butyl-ammonium chloride / 1,2-dichloro-ethane / 16 h / Inert atmosphere; Irradiation; Schlenk technique; Sealed tube

Reference： [1]Hartley, Will C.; Schiel, Florian; Ermini, Elena; Melchiorre, Paolo [Angewandte Chemie - International Edition, 2022, vol. 61, # 26][Angew. Chem., 2022, vol. 134, # 26]

50
[ 10538-51-9 ]
(E)-3-(2,5-dimethoxyphenyl)acrylic anhydride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Reflux; Schlenk technique;

Reference： [1]Hartley, Will C.; Schiel, Florian; Ermini, Elena; Melchiorre, Paolo [Angewandte Chemie - International Edition, 2022, vol. 61, # 26][Angew. Chem., 2022, vol. 134, # 26]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	10538-51-9	MDL No. :	MFCD00004378
Formula :	C₁₁H₁₂O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JPQWWJZORKTMIZ-ZZXKWVIFSA-N
M.W :	208.21	Pubchem ID :	697594
Synonyms :

Num. heavy atoms :	15
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.18
Num. rotatable bonds :	4
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	56.1
TPSA :	55.76 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) :	-6.31 cm/s

Log Po/w (iLOGP) :	2.06
Log Po/w (XLOGP3) :	1.78
Log Po/w (WLOGP) :	1.69
Log Po/w (MLOGP) :	1.3
Log Po/w (SILICOS-IT) :	1.79
Consensus Log Po/w :	1.72

[ CAS No. 10538-51-9 ]

Quality Control of [ 10538-51-9 ]

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Product Details of [ 10538-51-9 ]

Calculated chemistry of [ 10538-51-9 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 10538-51-9 ]

Application In Synthesis of [ 10538-51-9 ]

[ 10538-51-9 ] Synthesis Path-Upstream 1~1

[ 10538-51-9 ] Synthesis Path-Downstream 1~50

Related Functional Groups of
[ 10538-51-9 ]

Aryls

Alkenyls

Ethers

Carboxylic Acids

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 :	0.0
Bioavailability Score :	0.85

Log S (ESOL) :	-2.28
Solubility :	1.08 mg/ml ; 0.0052 mol/l
Class :	Soluble
Log S (Ali) :	-2.57
Solubility :	0.561 mg/ml ; 0.0027 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.12
Solubility :	1.57 mg/ml ; 0.00753 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.2

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313	UN#:	N/A
Hazard Statements:	H315-H319	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
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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.
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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.
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P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
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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
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
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. 10538-51-9 ]

Quality Control of [ 10538-51-9 ]

Related Doc. of [ 10538-51-9 ]

Product Details of [ 10538-51-9 ]

Calculated chemistry of [ 10538-51-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 10538-51-9 ]

Application In Synthesis of [ 10538-51-9 ]

[ 10538-51-9 ] Synthesis Path-Upstream 1~1

[ 10538-51-9 ] Synthesis Path-Downstream 1~50

Related Functional Groups of [ 10538-51-9 ]

Aryls

Alkenyls

Ethers

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 10538-51-9 ]