(2R,4S)-1-(tert-butoxycarbonyl)-4-propoxy-2-pyrrolidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】19046

【品名】(2R,4S)-1-(tert-butoxycarbonyl)-4-propoxy-2-pyrrolidinecarboxylic acid

【CA登记号】

【分子式】C₁₃H₂₃NO₅

【分子量】273.32936

【元素组成】C 57.13% H 8.48% N 5.12% O 29.27%

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)

Double alkylation of N-Boc-D-trans-4-hydroxyproline with allyl bromide in the presence of NaH in DMF afforded (II), which was subsequently hydrolyzed to the acid (III) with NaOH in aqueous methanol. Hydrogenation of allylic double bond in the presence of Pd/C gave propyl ether (IV).

参考文献中间体

合成目标

【1】 Kyle, D.J.; Hiner, R.N. (Scios Inc.); Bradykinin antagonist peptides. JP 1995504155; US 5385889 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	19043	(2R,4S)-1-(tert-butoxycarbonyl)-4-hydroxy-2-pyrrolidinecarboxylic acid	C₁₀H₁₇NO₅	详情	详情
(II)	19044	2-allyl 1-(tert-butyl) (2R,4S)-4-(allyloxy)-1,2-pyrrolidinedicarboxylate	C₁₆H₂₅NO₅	详情	详情
(III)	19045	(2R,4S)-4-(allyloxy)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid	C₁₃H₂₁NO₅	详情	详情
(IV)	19046	(2R,4S)-1-(tert-butoxycarbonyl)-4-propoxy-2-pyrrolidinecarboxylic acid	C₁₃H₂₃NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

In a solid phase synthesizer, an a-Boc-omega-Ts-Arg-phenylacetamidomethyl resin (V) was treated with trifluoroacetic acid (TFA) in anisole and dichloromethane in order to remove the Boc protecting group, and the resulting (VI) was coupled with Boc-octahydroindolecarboxylic acid (VII) in the presence of diisopropyl carbodiimide (DIPCDI) to give the dipeptide resin (VIII). This was submitted to successive coupling cycles (deprotection with TFA, and coupling with DIPCDI) to introduce sequentially the following amino acids: Boc-D-4-propoxyproline (IV), Boc-Ser(Bzl) (XIa) to yield the following resins: (IXa),(IXb) and (X), respectively.

参考文献中间体

合成目标

【1】 Kyle, D.J.; Hiner, R.N. (Scios Inc.); Bradykinin antagonist peptides. JP 1995504155; US 5385889 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIa)	16886	(2S)-3-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]propionic acid; N-alpha-t-BOC-o-benzyl-L-serine	23680-31-1	C₁₅H₂₁NO₅	详情	详情
(IXa)	19051	methyl (2S)-2-[[(2S,3aS,7aS)octahydro-1H-indol-2-ylcarbonyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoate		C₂₃H₃₅N₅O₅S	详情	详情
(IXb)	19052	methyl (2S)-2-[[((2S,3aS,7aS)-1-[[(2R,4S)-4-propoxypyrrolidinyl]carbonyl]octahydro-1H-indol-2-yl)carbonyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoate		C₃₁H₄₈N₆O₇S	详情	详情
(IV)	19046	(2R,4S)-1-(tert-butoxycarbonyl)-4-propoxy-2-pyrrolidinecarboxylic acid		C₁₃H₂₃NO₅	详情	详情
(V)	19047	methyl (2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoate		C₁₉H₃₀N₄O₆S	详情	详情
(VI)	19048	methyl (2S)-2-amino-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoate		C₁₄H₂₂N₄O₄S	详情	详情
(VII)	19049	(2S,3aS,7aS)-1-(tert-butoxycarbonyl)octahydro-1H-indole-2-carboxylic acid		C₁₄H₂₃NO₄	详情	详情
(VIII)	19050	tert-butyl (2S,3aS,7aS)-2-([[(1S)-4-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]-1-(methoxycarbonyl)butyl]amino]carbonyl)octahydro-1H-indole-1-carboxylate		C₂₈H₄₃N₅O₇S	详情	详情
(X)	19053	methyl (2S)-2-([[(2S,3aS,7aS)-1-([(2R,4S)-1-[(2S)-2-amino-3-(benzyloxy)propanoyl]-4-propoxypyrrolidinyl]carbonyl)octahydro-1H-indol-2-yl]carbonyl]amino)-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoate		C₄₁H₅₉N₇O₉S	详情	详情

Extended Information