methyl (3R,6S,9R,9aR)-6-[[(benzyloxy)carbonyl]amino]-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】35119

【品名】methyl (3R,6S,9R,9aR)-6-[[(benzyloxy)carbonyl]amino]-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylate

【CA登记号】

【分子式】C₁₉H₂₄N₂O₅S

【分子量】392.47604

【元素组成】C 58.15% H 6.16% N 7.14% O 20.38% S 8.17%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XXIII)

Cyclization of (XXIIa-b) employing ethyl chloroformate and triethylamine generated the thiazoloazepine (XXIII) as the major diastereoisomer. The methyl ester group of (XXIII) was then hydrolyzed with NaOH to provide the key intermediate (XXIV), which was finally converted to the title compound.

参考文献中间体

合成目标

【1】 Akasaka, K.; et al.; Synthesis of a new dual metalloprotease inhibitor.II. Stereoselective synthesis of peptidomimetic [5.7]-bycyclic compounds. Chem Pharm Bull 1999, 47, 11, 1532.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXIIa)	35117	(2S,5R)-2-[[(benzyloxy)carbonyl]amino]-5-[(2R,4R)-4-(methoxycarbonyl)-1,3-thiazolidin-2-yl]hexanoic acid	C₁₉H₂₆N₂O₆S	详情	详情
(XXIIb)	35118	(2S,5R)-2-[[(benzyloxy)carbonyl]amino]-5-[(2S,4R)-4-(methoxycarbonyl)-1,3-thiazolidin-2-yl]hexanoic acid	C₁₉H₂₆N₂O₆S	详情	详情
(XXIII)	35119	methyl (3R,6S,9R,9aR)-6-[[(benzyloxy)carbonyl]amino]-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylate	C₁₉H₂₄N₂O₅S	详情	详情
(XXIV)	35120	(3R,6S,9R,9aR)-6-[[(benzyloxy)carbonyl]amino]-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylic acid	C₁₈H₂₂N₂O₅S	详情	详情
(XXV)	35121	(3R,6S,9R,9aR)-6-amino-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylic acid	C₁₀H₁₆N₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Cyclization of (Xa, Xb) employing ethyl chloroformate and triethylamine generated the thiazoloazepine (XI) as the major diastereoisomer. Further hydrolysis of the methyl ester of (XI) with NaOH provided the key intermediate (XII). Finally, conversion to the title compound was accomplished by deprotection of the carbobenzoxy group of (XII) yielding (XIII), followed by coupling with S,S-2-acetylthio-3-methylpentanoic acid (XIV).

参考文献中间体

合成目标

【1】 Akasaka, K.; et al.; Synthesis of a new dual metalloprotease inhibitor.II. Stereoselective synthesis of peptidomimetic [5.7]-bycyclic compounds. Chem Pharm Bull 1999, 47, 11, 1532.
【2】 Naka, H.; Negi, S.; Shimomura, N.; Ikuta, H.; Naito, T.; Fukuda, Y.; Shimizu, H.; Tagami, K.; Akasaka, K.; Yoneda, N.; Kotake, M.; Akamatsu, K.; Matsui, M.; Matsushima, T.; Komatsu, Y.; Suda, S. (Eisai Co., Ltd.); Preparation method of (9R)-optically active isomers and intermediates therefor. JP 1998291992 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(Xa)	35117	(2S,5R)-2-[[(benzyloxy)carbonyl]amino]-5-[(2R,4R)-4-(methoxycarbonyl)-1,3-thiazolidin-2-yl]hexanoic acid		C₁₉H₂₆N₂O₆S	详情	详情
(Xb)	35118	(2S,5R)-2-[[(benzyloxy)carbonyl]amino]-5-[(2S,4R)-4-(methoxycarbonyl)-1,3-thiazolidin-2-yl]hexanoic acid		C₁₉H₂₆N₂O₆S	详情	详情
(XI)	35119	methyl (3R,6S,9R,9aR)-6-[[(benzyloxy)carbonyl]amino]-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylate		C₁₉H₂₄N₂O₅S	详情	详情
(XII)	35120	(3R,6S,9R,9aR)-6-[[(benzyloxy)carbonyl]amino]-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylic acid		C₁₈H₂₂N₂O₅S	详情	详情
(XIII)	35121	(3R,6S,9R,9aR)-6-amino-9-methyl-5-oxooctahydro[1,3]thiazolo[3,2-a]azepine-3-carboxylic acid		C₁₀H₁₆N₂O₃S	详情	详情
(XIV)	35122	(2S,3S)-2-(acetylsulfanyl)-3-methylpentanoic acid		C₈H₁₄O₃S	详情	详情

Extended Information