4-nitrobenzyl (2S,4S)-2-[(dimethylamino)carbonyl]-4-sulfanyl-1-pyrrolidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】22578

【品名】4-nitrobenzyl (2S,4S)-2-[(dimethylamino)carbonyl]-4-sulfanyl-1-pyrrolidinecarboxylate

【CA登记号】

【分子式】C₁₅H₁₉N₃O₅S

【分子量】353.39908

【元素组成】C 50.98% H 5.42% N 11.89% O 22.64% S 9.07%

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：(XIII)

The mercaptopyrrolidine (XIII) is prepared as follows: trans-4-hydroxy-L-proline (XV) is protected with 4-nitrobenzyl chloride (XVI) giving trans 4-hydroxy-N-(4-nitrobenzyloxycarbonyl)-L-proline (XVII), which is esterified with 4-methoxy benzyl chloride (XVIII) to the corresponding ester (XIX). The reaction of (XIX) with thioacetic acid by means of diethyl azodicarboxylate arid triphenyl-phosphine in THF affords the 4-acetylthio derivative (XX), which is partially hydrolyzed with trifluoroacetic acid and anisole to 4beta-(acetylthio)-N-(4-nitrobenzyloxycarbonyl)pyrrolidine-2beta-carboxylic acid (XXI). The condensation of (XXI) with dimethylamine by means of dicyclohexylcarbodiimide (DCC) gives the fully protected dimethylamide (XXII), which is deacetylated with NaOH in water to atford the desired product (XIII).

参考文献中间体

合成目标

【1】 Fukasawa, M.; Inoue, T.; Kato, M.; Matsumura, H.; Sunagawa, M. (Sumitomo Pharmaceuticals Co., Ltd.); Thiopyrrolidinyl-beta-lactam derivs.. EP 0126587; ES 8600305; JP 1985001186; JP 1985019787; JP 1991041066; US 4933333; US 4943569; US 5122604 .
【2】 Prous, J.; Castaner, J.; SM-7338. Drugs Fut 1988, 13, 6, 534.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12893	Ethanethioic S-acid		C₂H₄OS	详情	详情
(XIII)	22578	4-nitrobenzyl (2S,4S)-2-[(dimethylamino)carbonyl]-4-sulfanyl-1-pyrrolidinecarboxylate		C₁₅H₁₉N₃O₅S	详情	详情
(XV)	14489	(2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid; L-Hydroxyproline	51-35-4	C₅H₉NO₃	详情	详情
(XVI)	22580	1-(chloromethyl)-4-nitrobenzene	100-14-1	C₇H₆ClNO₂	详情	详情
(XVII)	22581	(2S,4R)-4-hydroxy-1-[[(4-nitrobenzyl)oxy]carbonyl]-2-pyrrolidinecarboxylic acid		C₁₃H₁₄N₂O₇	详情	详情
(XVIII)	11910	4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether	824-94-2	C₈H₉ClO	详情	详情
(XIX)	22583	2-(4-methoxybenzyl) 1-(4-nitrobenzyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate		C₂₁H₂₂N₂O₈	详情	详情
(XX)	22584	2-(4-methoxybenzyl) 1-(4-nitrobenzyl) (2S,4S)-4-(acetylsulfanyl)-1,2-pyrrolidinedicarboxylate		C₂₃H₂₄N₂O₈S	详情	详情
(XXI)	18241	(2S,4S)-4-(acetylsulfanyl)-1-[[(4-nitrobenzyl)oxy]carbonyl]-2-pyrrolidinecarboxylic acid		C₁₅H₁₆N₂O₇S	详情	详情
(XXII)	22586	4-nitrobenzyl (2S,4S)-4-(acetylsulfanyl)-2-[(dimethylamino)carbonyl]-1-pyrrolidinecarboxylate		C₁₇H₂₁N₃O₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

The condensation of (XII) with 1-(4-nitrobenzyloxycarbonyl)-2beta-(dimethylaminocarbonyl)-4beta-mercaptopyrrolidine (XIII) in acetonitrile affords the di(4-nitrobenzyl) derivative (XIV), which is finally debencilated by hydrogenation with H2 over Pd/C in THF.

参考文献中间体

合成目标

【1】 Fukasawa, M.; Inoue, T.; Kato, M.; Matsumura, H.; Sunagawa, M. (Sumitomo Pharmaceuticals Co., Ltd.); Thiopyrrolidinyl-beta-lactam derivs.. EP 0126587; ES 8600305; JP 1985001186; JP 1985019787; JP 1991041066; US 4933333; US 4943569; US 5122604 .
【2】 Prous, J.; Castaner, J.; SM-7338. Drugs Fut 1988, 13, 6, 534.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XII)	22577	4-nitrobenzyl (5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₂₉H₂₇N₂O₁₀P	详情	详情
(XIII)	22578	4-nitrobenzyl (2S,4S)-2-[(dimethylamino)carbonyl]-4-sulfanyl-1-pyrrolidinecarboxylate	C₁₅H₁₉N₃O₅S	详情	详情
(XIV)	22587	4-nitrobenzyl (5S,6S)-3-[((3S,5S)-5-[(dimethylamino)carbonyl]-1-[[(4-nitrobenzyl)oxy]carbonyl]pyrrolidinyl)sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₃₂H₃₅N₅O₁₁S	详情	详情

Extended Information