tert-butyl (2S)-2-amino-3-phenylpropanoate -Drug Synthesis Database

【结构式】

【分子编号】60837

【品名】tert-butyl (2S)-2-amino-3-phenylpropanoate

【CA登记号】

【分子式】C₁₃H₁₉NO₂

【分子量】221.2994

【元素组成】C 70.56% H 8.65% N 6.33% O 14.46%

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：(III)

N-Boc-L-Phenylalanine (I) is converted into the tert-butyl ester (II) upon treatment with tert-butyl trichloroacetimidate and boron trifluoride. Then, selective removal of the N-Boc group of (II) with HCl in EtOAc provides L-phenylalanine ester (III). Coupling of (III) with N-Cbz-2-methylproline (IV) furnishes dipeptide (V). After hydrogenolysis of the N-Cbz group of (V), the resultant amine (VI) is acylated by means of 3,5-dichlorobenzenesulfonyl chloride (VII), yielding sulfonamide (VIII). The tert-butyl ester group of (VIII) is finally cleaved by treatment with trifluoroacetic acid in CH2Cl2

参考文献中间体

合成目标

【1】 Hagmann, W.K.; Durette, P.L.; Mumford, R.A.; Mills, S.G.; Kevin, N.J.; Schmidt, J.A.; MacCoss, M.; Van Riper, G.M. (Merck & Co., Inc.); Heterocyclic amide cpds. as cell adhesion inhibitors. EP 1001764; WO 9853814 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	61667	tert-butyl 2,2,2-trichloroethanimidoate	C₆H₁₀Cl₃NO	详情	详情
(I)	22184	(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid	C₁₄H₁₉NO₄	详情	详情
(II)	60836	tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate	C₁₈H₂₇NO₄	详情	详情
(III)	60837	tert-butyl (2S)-2-amino-3-phenylpropanoate	C₁₃H₁₉NO₂	详情	详情
(IV)	60838	(2S)-1-[(benzyloxy)carbonyl]-2-methyl-2-pyrrolidinecarboxylic acid	C₁₄H₁₇NO₄	详情	详情
(V)	60839	benzyl (2S)-2-({[(1S)-1-benzyl-2-(tert-butoxy)-2-oxoethyl]amino}carbonyl)-2-methyl-1-pyrrolidinecarboxylate	C₂₇H₃₄N₂O₅	详情	详情
(VI)	60840	tert-butyl (2S)-2-({[(2S)-2-methylpyrrolidinyl]carbonyl}amino)-3-phenylpropanoate	C₁₉H₂₈N₂O₃	详情	详情
(VII)	59023	3,5-dichlorobenzenesulfonyl chloride	C₆H₃Cl₃O₂S	详情	详情
(VIII)	60841	tert-butyl (2S)-2-[({(2S)-1-[(3,5-dichlorophenyl)sulfonyl]-2-methylpyrrolidinyl}carbonyl)amino]-3-phenylpropanoate	C₂₅H₃₀Cl₂N₂O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Acylation of L-phenylalanine tert-butyl ester (I) with 2,4-dichlorobenzoyl chloride (II) provides the corresponding amide (III). This is then N-alkylated with 3-nitrobenzyl bromide (IV) in the presence of NaH to yield (V). The tert-butyl ester group of (V) is finally cleaved with trifluoroacetic acid to furnish the target carboxylic acid. (1-3)

参考文献中间体

合成目标

【1】 Chan, L.; Reddy, J.; Proulx, M.; Das, S.K.; Pereira, O.; Wang, W.; Siddiqui, A.; Yannopoulos, C.G.; Poisson, C.; Turcotte, N.; Drouin, A.; Alaoui-Ismaili, M.H.; Bethell, R.; Hamel, M.; L'Heureux, L.; Bilimoria, D.; Nguyen-Ba, N.; Identification of N,N-disubstituted phenylalanines as a novel class of inhibitors of hepatitis C NS5B polymerase. J Med Chem 2003, 46, 8, 1283.
【2】 Proulx, M.; Chan, L.; Reddy, T.J.; Das, S.K.; Pereira, O.Z.; Identification of a novel class of inhibitors of hepatitis C NS5B polymerase. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 40.
【3】 Pereira, O.Z.; Wang, W.; Siddiqui, M.A.; Bedard, J.; Nguyen Ba, N.; Chan, C.K.L.; Das, S.K.; Shuttleworth, S. (Shire BioChem Inc.); Cpds. and methods for the treatment or prevention of flavivirus infections. US 2003229053; WO 02100846 .

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)	60837	tert-butyl (2S)-2-amino-3-phenylpropanoate		C₁₃H₁₉NO₂	详情	详情
(II)	35131	2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride	89-75-8	C₇H₃Cl₃O	详情	详情
(III)	64057	1,1-dimethylethyl 2-{[(2,4-dichlorophenyl)carbonyl]amino}-3-phenylpropanoate		C₂₀H₂₁Cl₂NO₃	详情	详情
(IV)	19636	1-(bromomethyl)-3-nitrobenzene	3958-57-4	C₇H₆BrNO₂	详情	详情
(V)	64058	1,1-dimethylethyl 2-{[(2,4-dichlorophenyl)carbonyl][(3-nitrophenyl)methyl]amino}-3-phenylpropanoate		C₂₇H₂₆Cl₂N₂O₅	详情	详情

Extended Information