(2S,3S)-3-amino-2-hydroxyheptanamide -Drug Synthesis Database

【结构式】

【分子编号】47880

【品名】(2S,3S)-3-amino-2-hydroxyheptanamide

【CA登记号】

【分子式】C₇H₁₆N₂O₂

【分子量】160.21632

【元素组成】C 52.48% H 10.07% N 17.48% O 19.97%

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：(IX)

The resin-bound aminohydroxyacid (IX) was prepared as follows. 2-Heptenoic acid (I) was converted to the corresponding tert-butyl ester (II) upon treatment with dimethylformamide di-tert-butylacetal. Conjugate addition to (II) of the chiral amine (III) followed by oxidative treatment with (+)-(camphorsulfonyl)oxaziridine then furnished the amino hydroxyester (IV). Hydrogenolytic cleavage of the N-benzyl groups of (IV) produced the primary amine (V), which was subsequently protected as the N-Fmoc derivative (VI) by using O-Fmoc-hydroxysuccinimide. Tert-butyl ester cleavage in (VI) by means of trifluoroacetic acid gave carboxylic acid (VII). This was then attached to Rink resin using TBTU as the coupling reagent to yield resin (VIII). Deprotection of the N-Fmoc group of (VIII) with piperidine in DMF produced the resin-bound aminohydroxyacid (IX).

参考文献中间体

合成目标

【1】 Jones, P.S.; Kay, P.B.; Wilson, F.X.; Raynham, T.M.; Hurst, D.N. (Hoffmann-La Roche, Inc.); alpha-Ketoamide derivs.. US 6187905 .

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)	47873	(E)-2-heptenoic acid	10352-88-2	C₇H₁₂O₂	详情	详情
(II)	47874	tert-butyl (E)-2-heptenoate		C₁₁H₂₀O₂	详情	详情
(III)	47881	(1R)-N-benzyl-1-phenyl-1-ethanamine; N-benzyl-N-[(1R)-1-phenylethyl]amine		C₁₅H₁₇N	详情	详情
(IV)	47875	tert-butyl (2S,3S)-3-[benzyl[(1R)-1-phenylethyl]amino]-2-hydroxyheptanoate		C₂₆H₃₇NO₃	详情	详情
(V)	47876	tert-butyl (2S,3S)-3-amino-2-hydroxyheptanoate		C₁₁H₂₃NO₃	详情	详情
(VI)	47877	tert-butyl (2S,3S)-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2-hydroxyheptanoate		C₂₆H₃₃NO₅	详情	详情
(VII)	47878	(2S,3S)-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2-hydroxyheptanoic acid		C₂₂H₂₅NO₅	详情	详情
(VIII)	47879	9H-fluoren-9-ylmethyl (1S)-1-[(1S)-2-amino-1-hydroxy-2-oxoethyl]pentylcarbamate		C₂₂H₂₆N₂O₄	详情	详情
(IX)	47880	(2S,3S)-3-amino-2-hydroxyheptanamide		C₇H₁₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

N-Fmoc-L-leucine (X) was coupled to the resin (IX) by means of TBTU to afford, after Fmoc deprotection with piperidine/DMF, the dipeptide-resin (XI). Sequential chain elongation by coupling with the following protected amino acids: Fmoc-3-methyl-L-valine (A), Fmoc-2-methyl-L-phenylalanine (B), Fmoc-L-glutamic gamma-tert-butyl ester (C), and Fmoc-L-aspartic beta-tert-butyl ester (D), followed by the corresponding Fmoc deprotection steps, furnished the peptide resins (XII), (XIII), (XIV) and (XV), respectively.

参考文献中间体

合成目标

【1】 Jones, P.S.; Kay, P.B.; Wilson, F.X.; Raynham, T.M.; Hurst, D.N. (Hoffmann-La Roche, Inc.); alpha-Ketoamide derivs.. US 6187905 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	22255	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(2-methylphenyl)propionic acid		C₂₅H₂₃NO₄	详情	详情
(D)	22260	(2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid		C₂₃H₂₅NO₆	详情	详情
(A)	43350	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3,3-dimethylbutyric acid	132684-60-7	C₂₁H₂₃NO₄	详情	详情
(IX)	47880	(2S,3S)-3-amino-2-hydroxyheptanamide		C₇H₁₆N₂O₂	详情	详情
(X)	19934	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoic acid		C₂₁H₂₃NO₄	详情	详情
(XI)	47882	(2S,3S)-3-[[(2S)-2-amino-4-methylpentanoyl]amino]-2-hydroxyheptanamide		C₁₃H₂₇N₃O₃	详情	详情
(XII)	47883	(2S,3S)-3-[((2S)-2-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-4-methylpentanoyl)amino]-2-hydroxyheptanamide		C₁₉H₃₈N₄O₄	详情	详情
(XIII)	47884	(2S,3S)-3-([(2S)-2-[((2S)-2-[[(2S)-2-amino-3-(2-methylphenyl)propanoyl]amino]-3,3-dimethylbutanoyl)amino]-4-methylpentanoyl]amino)-2-hydroxyheptanamide		C₂₉H₄₉N₅O₅	详情	详情
(XIV)	47885	tert-butyl (4S,7S,10S,13S,16S)-4-amino-16-[(1S)-2-amino-1-hydroxy-2-oxoethyl]-10-(tert-butyl)-13-isobutyl-7-(2-methylbenzyl)-5,8,11,14-tetraoxo-6,9,12,15-tetraazaicosan-1-oate		C₃₈H₆₄N₆O₈	详情	详情
(XV)	47886	tert-butyl (3S,6S,9S,12S,15S,18S)-3-amino-18-[(1S)-2-amino-1-hydroxy-2-oxoethyl]-6-[3-(tert-butoxy)-3-oxopropyl]-12-(tert-butyl)-15-isobutyl-9-(2-methylbenzyl)-4,7,10,13,16-pentaoxo-5,8,11,14,17-pentaazadocosan-1-oate		C₄₆H₇₇N₇O₁₁	详情	详情
(C)	22258	(2S)-5-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxopentanoic acid	104091-08-9	C₂₄H₂₇NO₆	详情	详情

Extended Information