【结 构 式】 |
【分子编号】12776 【品名】methyl 2-(2-chlorophenyl)-2-[[2-(2-thienyl)ethyl]amino]acetate 【CA登记号】 |
【 分 子 式 】C15H16ClNO2S 【 分 子 量 】309.81628 【元素组成】C 58.15% H 5.21% Cl 11.44% N 4.52% O 10.33% S 10.35% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The title product can be obtained in several steps: 1) (+)-2-(2-Chlorophenyl)glycine methyl ester [(+)-IV] is prepared as follows: a) Racemic 2-(2-chlorophenyl)glycine (I) is methylated with methanol - HCl to the methyl ester (II), which is resolved with (+)-tartaric acid to the active ester [(+)-IV]. b) Racemic (I) is resolved with (+)-10-camphorsulfonic acid to (+)-2-(2-chlorophenyl)glycine [(+)-III], which is then esterified as before to [(+)-IV]. 2) (+)-2-(2-Chlorophenyl)-N-[2-(2-thienyl)ethyl]glycine methyl ester [(+)-VII] is prepared as follows: a) Alkylation of [(+)-IV] with 2-[2-(phenylsulfonyloxy)ethyl]thiophene (V) or with 2-(2-bromoethyl)thiophene (VI). b) Optical resolution of racemic alkylated glycine ester (VIII) with (+)-10-camphorsulfonic acid. 3) Finally, (+)-clopidogrel is prepared as follows: a) Cyclization of active [(+)-VII] with formaldehyde - formic acid and aqueous HCl. b) Cyclization of racemic (VIII) as before, yielding racemic clopidogrel (PCR-4099), followed by optical resolution with (+)-10-camphorsulfonic acid.
【1】 Descamps, M.; Radisson, J. (Sanofi); Process for the preparation of an N-phenylacetic deriv. of tetrahydrothieno(3,2-c)pyridine and its intermediate of synthesis. EP 0446569 . |
【2】 Badorc, A.; Frehel, D. (Sanofi-Synthélabo ); Dextrorotatory enantiomer of methyl alpha-(4,5,6,7-tetrahydrothieno[3,2-c]pyrid-5-yl)(2-chlorophenyl)acetate process for its preparation and pharmaceutical compsns. containing it. AU 8811292; EP 0281459; FR 2612929; FR 2623810; JP 1988203684; US 4847265 . |
【3】 Aubert, D.; Ferrand, C.; Maffrand, J.-P. (Sanofi-Synthelabo ); Novel thieno(3,2-c)pyridine derivs., process for their preparation and their application in therapy. EP 0099802; US 4529596 . |
【4】 Savi, P.; Maffrand, J.P.; Defreyn, G.; Frehel, D.; Badorc, A.; Herbert, J.M.; Kieffer, G.; Bernat, A.; Delebassee, D.; Clopidogrel Hydrogensulfate. Drugs Fut 1993, 18, 2, 107. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
((+)-IV) | 12772 | methyl (2S)-2-amino-2-(2-chlorophenyl)ethanoate | 141109-14-0 | C9H10ClNO2 | 详情 | 详情 |
((+)-VII) | 12775 | methyl (2S)-2-(2-chlorophenyl)-2-[[2-(2-thienyl)ethyl]amino]ethanoate | 141109-20-8 | C15H16ClNO2S | 详情 | 详情 |
PCR 4099 (+/-) | 63476 | methyl 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetate | C16H16ClNO2S | 详情 | 详情 | |
(I) | 12769 | 2-Amino-2-(2-chlorophenyl)acetic acid | 88744-36-9 | C8H8ClNO2 | 详情 | 详情 |
(II) | 12770 | methyl 2-amino-2-(2-chlorophenyl)acetate | C9H10ClNO2 | 详情 | 详情 | |
(III) | 12771 | (2S)-2-Amino-2-(2-chlorophenyl)ethanoic acid | 141315-50-6 | C8H8ClNO2 | 详情 | 详情 |
(V) | 12773 | 2-(2-thienyl)ethyl benzenesulfonate | C12H12O3S2 | 详情 | 详情 | |
(VI) | 12774 | 2-(2-Bromoethyl)thiophene | 26478-16-0 | C6H7BrS | 详情 | 详情 |
(VIII) | 12776 | methyl 2-(2-chlorophenyl)-2-[[2-(2-thienyl)ethyl]amino]acetate | C15H16ClNO2S | 详情 | 详情 |