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【结 构 式】 
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【分子编号】52697 【品名】(Z)-7-{(1R,2R,3S,5R)-6,6-dimethyl-2-[({5-[(phenylsulfonyl)oxy]-1-benzothiophen-3-yl}carbonyl)amino]bicyclo[3.1.1]hept-3-yl}-5-heptenoic acid 【CA登记号】 |
【 分 子 式 】C31H35NO6S2 【 分 子 量 】581.75404 【元素组成】C 64% H 6.06% N 2.41% O 16.5% S 11.02% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)Amino alcohol (XXVIII) was acylated with acid chloride (X) under Schotten-Baumann conditions to afford amide (XXX). Subsequent conversion of the primary alcohol (XXX) to aldehyde (XXXI) was accomplished by either Swern oxidation or by treatment with NaOCl in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Wittig condensation of aldehyde (XXXI) with the ylide generated from (4-carboxybutyl)triphenylphosphonium bromide (XXXII) in the presence of potassium tert-butoxide furnished the Z-olefin (XXXIII). Finally, basic hydrolysis of the benzenesulfonyl protecting group of (XXXIII) yielded the title compound.
| 【1】 Arimura, A.; Honma, T.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Benzothiophenecarboxamide derivs. and PGD2 antagonists comprising them. EP 0944614; JP 2000514824; US 6083974; WO 9825919 . |
| 【2】 Okada, T.; Honma, T.; Kakinuma, M.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Process for producing benzothiophenecarboxylic acid amide derivs.. EP 1069123; WO 9950261 . |
| 【3】 Hiramatsu, Y.; Honma, T. (Shionogi & Co. Ltd.); Process for producing 5-hydroxybenzo[b]thiophene-3-carboxylic acid derivs.. EP 1069122; WO 9950260 . |
| 【4】 Cai, D.; Larsen, R.; Journet, M.; Campos, K. (Merck & Co., Inc.); Process for the preparation of PGD2 antagonist. WO 0232892 . |
| 【5】 Hiramatsu, Y.; Honma, T.; Mitsumori, S. (Shionogi & Co. Ltd.); Novel process for producing bicyclic amino alcohol. EP 1193243; WO 0102334 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 52252 | 3-(chlorocarbonyl)-1-benzothiophen-5-yl benzenesulfonate | C15H9ClO4S2 | 详情 | 详情 | |
| (XXVIII) | 52250 | 2-(2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl)-1-ethanol | C11H21NO | 详情 | 详情 | |
| (XXX) | 52253 | 3-({[3-(2-hydroxyethyl)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]amino}carbonyl)-1-benzothiophen-5-yl benzenesulfonate | C26H29NO5S2 | 详情 | 详情 | |
| (XXXI) | 52254 | 3-({[6,6-dimethyl-3-(2-oxoethyl)bicyclo[3.1.1]hept-2-yl]amino}carbonyl)-1-benzothiophen-5-yl benzenesulfonate | C26H27NO5S2 | 详情 | 详情 | |
| (XXXII) | 23582 | (4-carboxybutyl)(triphenyl)phosphonium | C23H24O2P | 详情 | 详情 | |
| (XXXIII) | 52697 | (Z)-7-{(1R,2R,3S,5R)-6,6-dimethyl-2-[({5-[(phenylsulfonyl)oxy]-1-benzothiophen-3-yl}carbonyl)amino]bicyclo[3.1.1]hept-3-yl}-5-heptenoic acid | C31H35NO6S2 | 详情 | 详情 |