S-[(3R)-5-oxotetrahydro-1H-pyrrol-3-yl] ethanethioate -Drug Synthesis Database

【结构式】

【分子编号】17191

【品名】S-[(3R)-5-oxotetrahydro-1H-pyrrol-3-yl] ethanethioate

【CA登记号】

【分子式】C₆H₉NO₂S

【分子量】159.209

【元素组成】C 45.27% H 5.7% N 8.8% O 20.1% S 20.14%

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：(IV)

1) The mesylation of 4(S)-hydroxypyrrolidin-2-one (I) with mesyl chloride and triethylamine in pyridine gives the corresponding ester (II), which is treated with potassium thioacetate (III) in refluxing acetonitrile yielding 4(R)-(acetylsulfanyl)pyrrolidin-2-one (IV). The hydrolysis of (IV) with sodium methoxide in methanol followed by acidification with aqueous HCl affords 4(R)-sulfanylpyrrolidin-2-one (V), which is condensed with (1R,5S,6S)-2-(diphenoxyphosphoryloxy)-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid p-nitrobenzyl ester (VI) by means of ethyldiisopropylamine in acetonitrile to give (1R,5S,6S)-6-[1(R)-hydroxyethyl]-1-methyl-2-[5-oxopyrrolidin-3(R)-ylsulfanyl]-1-carba-2-penem-3-carboxylic acid p-nitrobenzyl ester (VII). The hydrogenolysis of (VII) with H2 over Pd/C in THF/aqueous phosphate buffer yields the sodium salt (VIII), which is finally esterified with pivaloyloxymethyl iodide (IX) in dimethylacetamide.

参考文献中间体

合成目标

【1】 Yasuda, H.; Kuwahara, S.; Kawamoto, I.; Miyauchi, M.; Endo, R.; Hisaoka, M.; CS-834, a new oral carbapenem: I. Structure-activity relationships of 2-substituted 1beta-methylcarbapenems. 36th Intersci Conf Antimicrob Agents Chemother (Sept 15-18, New Orleans) 1996, Abst F105.
【2】 Endo, R.; Yasuda, H.; Kawamoto, I.; Hisaoka, M.; Miyauchi, M.; Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834. J Antibiot 1997, 50, 5, 429-39.
【3】 Graul, A.; Castañer, R.M.; Castañer, J.; Leeson, P.; CS-834. Drugs Fut 1998, 23, 3, 261.
【4】 Kawamoto, I.; Tanaka, T.; Endo, R.; Miyauchi, M.; Iwata, M. (Sankyo Co., Ltd.); 2-(Heterocyclylthio)carbapenem derivs. their preparation and their use as antibiotics. AU 8932386; EP 0337637; EP 0597821; JP 1990028180; JP 1990049783; US 5104867; US 5242914 .
【5】 Kawamoto, I.; Miyauchi, M.; Endo, R. (Sankyo Co., Ltd.); Crystalline carbapenem deriv. EP 0599512; JP 1995165759 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	17188	(S)-4-hydroxy-2-pyrrolidone; (4S)-4-hydroxytetrahydro-2H-pyrrol-2-one; (S)-4-hydroxypyrrolidone	68108-18-9	C₄H₇NO₂	详情	详情
(II)	17189	(3S)-5-oxotetrahydro-1H-pyrrol-3-yl methanesulfonate		C₅H₉NO₄S	详情	详情
(III)	17190	potassium ethanethioate	10387-40-3	C₂H₃KOS	详情	详情
(IV)	17191	S-[(3R)-5-oxotetrahydro-1H-pyrrol-3-yl] ethanethioate		C₆H₉NO₂S	详情	详情
(V)	17192	(4R)-4-sulfanyltetrahydro-2H-pyrrol-2-one	157429-42-0	C₄H₇NOS	详情	详情
(VI)	13224	4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	90776-59-3	C₂₉H₂₇N₂O₁₀P	详情	详情
(VII)	17194	4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3R)-5-oxotetrahydro-1H-pyrrol-3-yl]sulfanyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₁H₂₃N₃O₇S	详情	详情
(VIII)	17195	sodium (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3R)-5-oxopyrrolidinyl]sulfanyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₁₄H₁₇N₂NaO₅S	详情	详情
(IX)	11159	iodomethyl pivalate		C₆H₁₁IO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The original procedure for the synthesis of the intermediate (R)-4-mercaptopyrrolidine-2-thione (IV) started from (S)-4-hydroxy-2-pyrrolidinone (I). Mitsunobu coupling with thioacetic acid produced the (R)-thioacetate ester (II). Conversion of (II) to the thiolactam (III) was achieved by treatment with Lawesson's reagent. The thioester group of (III) was then hydrolyzed by means of methanolic ammonia.

参考文献中间体

合成目标

【1】 Iwasaki, T.; Kondo, K.; Horikawa, H.; Yamaguchi, T.; Matsushita, T. (Tanabe Seiyaku Co., Ltd.); 1-Methylcarbapenem derivs. and process for preparation thereof. EP 0474243; JP 1992279588; US 5153187 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	17188	(S)-4-hydroxy-2-pyrrolidone; (4S)-4-hydroxytetrahydro-2H-pyrrol-2-one; (S)-4-hydroxypyrrolidone	68108-18-9	C₄H₇NO₂	详情	详情
(II)	17191	S-[(3R)-5-oxotetrahydro-1H-pyrrol-3-yl] ethanethioate		C₆H₉NO₂S	详情	详情
(III)	37711	S-[(3R)-5-thioxopyrrolidinyl] ethanethioate		C₆H₉NOS₂	详情	详情
(IV)	37712	(4R)-4-sulfanyl-2-pyrrolidinethione		C₄H₇NS₂	详情	详情

Extended Information