(2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】33552

【品名】(2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylic acid

【CA登记号】65167-28-4

【分子式】C₁₁H₁₇NO₄S

【分子量】259.32632

【元素组成】C 50.95% H 6.61% N 5.4% O 24.68% S 12.37%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

It is prepared by hydrolysis with ammonia in methanol of N-(3-acetylthio-2-methylpropanoyl)-L-proline (I). Compound (I) can be obtained in three different ways: 1) The reaction of L-proline tert-butyl ester (II) with 3-acetylthio-2-methyl-propanoic acid (III) by means of dicyclohexylcarbodiimide in CH2Cl2 gives N-(3-acetylthio-2-methylpropanoyl)-L-proline tert-butyl ester (IV), which is hydrolyzed with trifluoroacetic acid in anisole. 2) By condensation of L-proline (V) with 3-acetylthio-2-methylpropanoyl chloride (VI) (prepared from the corresponding acid (III) with SOCl2) by means of NaOH in water. 3) The condensation of L-proline (V) with methacryloyl chloride (VII) by means of NaHCO3 in water yields N-methacryloyl-L-proline (VIII), which is then treated with thiolacetic acid (A) and azobisisobutyronitrile. The acid (III) is obtained by addition of thiolacetic acid (IX) to methacrylic acid (X) at 100 C.

参考文献中间体

合成目标

【1】 Cushman, D.W.; Ondetti, M.A.; Azetidine-2-carboxylic acid derivatives. BE 0851361; DD 283999; JP 58189113; JP 58189158; US 4046889; US 4154840 .
【2】 Roberts, P.J.; Castaner, J.; Captopril. Drugs Fut 1978, 3, 11, 795.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	33555	Thiolacetic acid; Thioacetic acid; ethanethioic O-acid; Ethanethioic acid	507-09-5	C₂H₄OS	详情	详情
(I)	33552	(2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylic acid	65167-28-4	C₁₁H₁₇NO₄S	详情	详情
(II)	19832	tert-butyl (2S)-2-pyrrolidinecarboxylate		C₉H₁₇NO₂	详情	详情
(III)	33556	3-(acetylsulfanyl)-2-methylpropionic acid		C₆H₁₀O₃S	详情	详情
(IV)	33551	tert-butyl (2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylate		C₁₅H₂₅NO₄S	详情	详情
(V)	16731	L-proline	147-85-3	C₅H₉NO₂	详情	详情
(VI)	33557	S-(3-chloro-2-methyl-3-oxopropyl) ethanethioate		C₆H₉ClO₂S	详情	详情
(VII)	33553	2-methylacryloyl chloride	920-46-7	C₄H₅ClO	详情	详情
(VIII)	33554	(2S)-1-methacryloyl-2-pyrrolidinecarboxylic acid		C₉H₁₃NO₃	详情	详情
(IX)	12893	Ethanethioic S-acid		C₂H₄OS	详情	详情
(X)	33550	2-methylacrylic acid	79-41-4	C₄H₆O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【2】刘仁涌，李慧琴，刘春庆，等.卡托普利合成方法的改进.沈阳药科大学学报，1997,14:262.
【1】 Nam DH,Lee CS,Ryu DDY.An improved synthesis of captopril.J Pharm Sci,1984,73:1843.

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)	33552	(2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylic acid	65167-28-4	C₁₁H₁₇NO₄S	详情	详情
(II)	69581	3-Chloro-2-methylpropionicacid;b-Chloroisobutyric acid;3-chloro-2-methylpropanoic acid	16674-04-7	C₄H₇ClO₂	详情	详情
(III)	69582	3-chloro-2-methylpropanoyl chloride		C₄H₆Cl₂O	详情	详情
(IV)	16731	L-proline	147-85-3	C₅H₉NO₂	详情	详情
(V)	69583	(S)-1-((S)-3-chloro-2-methylpropanoyl)pyrrolidine-2-carboxylic acid		C₉H₁₄ClNO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Kinoshita K,Kanou F,Okubo T,et al.Simple process for producting high-quality captopril:WO,Patent 9,816,509,1998.

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)	33552	(2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylic acid	65167-28-4	C₁₁H₁₇NO₄S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Hen AC.Process for the preparation of 1-[3-acetylthio-2(S)-methylpropanoyl]-L-proline:US,Patnet 5,387,697,1995.
【2】 Sakashita K,Sato E,Sakimase A,et al.Production of L-proline derivative:JP,Patent 05,221,966,1993.
【3】 Kobayashi Y,Tosa K,Sakimase A,et al.Process for the preparation of L-proline derivatives:EP,Patent 507,095,1992.

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)	16731	L-proline	147-85-3	C₅H₉NO₂	详情	详情
(II)	28852	(2R)-3-Acetylthio-2-methylpropionyl chloride;L-3-(Acetylthio)-2-methylpropanoyl chloride ;S-[(2R)-3-chloro-2-methyl-3-oxopropyl] ethanethioate	74345-73-6	C₆H₉ClO₂S	详情	详情
(III)	33552	(2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylic acid	65167-28-4	C₁₁H₁₇NO₄S	详情	详情

Extended Information