benzyl (2S)-2-amino-3-phenylpropanoate；L-phenylalanine benzyl ester -Drug Synthesis Database

【结构式】

【分子编号】27693

【品名】benzyl (2S)-2-amino-3-phenylpropanoate；L-phenylalanine benzyl ester

【CA登记号】

【分子式】C₁₆H₁₇NO₂

【分子量】255.31652

【元素组成】C 75.27% H 6.71% N 5.49% O 12.53%

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)

By deprotection of tripeptide (V) (hydrogenolysis of the benzyl group with H2 over Pd/C) followed by condensation with amino acid ester (XI) by means of diethyl cyanophosphonate (DECP) in DMF. The intermediates (V) and (XI) have been obtained as follows: 1.- The condensation of N-(tert-butoxycarbonyl)-L-valine (I) with L-leucine benzyl ester (II) by means of DCC, NMM and NHS gives the dipeptide (III), which is condensed with L-phenylalanine benzyl ester (IV) by first debenzylation and condensation as before yielding the desired tripeptide (V). 2.- The cyclization of N-(tert-butoxycarbonyl)-L-glutamine (VI) by means of DCC and NHS gives the glutarimide (VII), which is partially reduced with NaBH4 to the cyclic Boc-glutaminal (VIII). The condensation of (VIII) with the phosphonate (IX) by means of NaH in THF affords the unsaturated protected aminoester (X), which is finally deprotected with trifluoroacetic acid in dichloromethane providing the desired amino acid ester (XI).

参考文献中间体

合成目标

【1】 Shepherd, T.A.; Furness, K.; Venkatraman, S.; Wang, Q.M.; Aubé, J.; Nimkar, S.; Kong, J.; Hanzlik, R.P.; Synthesis and evaluation of peptidyl Michael acceptors that inactivate human rhinovirus 3C protease and inhibit virus replication. J Med Chem 1998, 41, 14, 2579.

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)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(II)	27691	benzyl (2S)-2-amino-5-methylhexanoate		C₁₄H₂₁NO₂	详情	详情
(III)	27692	benzyl (2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)-5-methylhexanoate		C₂₄H₃₈N₂O₅	详情	详情
(IV)	27693	benzyl (2S)-2-amino-3-phenylpropanoate；L-phenylalanine benzyl ester		C₁₆H₁₇NO₂	详情	详情
(V)	27694	benzyl (6S,9S,12S)-12-benzyl-9-isopentyl-6-isopropyl-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate		C₃₃H₄₇N₃O₆	详情	详情
(VI)	27695	(2S)-6-amino-2-[(tert-butoxycarbonyl)amino]-6-oxohexanoic acid		C₁₁H₂₀N₂O₅	详情	详情
(VII)	27696	tert-butyl (3S)-2,6-dioxopiperidinylcarbamate		C₁₀H₁₆N₂O₄	详情	详情
(VIII)	27697	tert-butyl (3S)-2-hydroxy-6-oxopiperidinylcarbamate		C₁₀H₁₈N₂O₄	详情	详情
(IX)	27698	methyl 2-(diethoxyphosphoryl)acetate	1067-74-9	C₇H₁₅O₅P	详情	详情
(X)	27699	methyl (E,4S)-8-amino-4-[(tert-butoxycarbonyl)amino]-8-oxo-2-octenoate		C₁₄H₂₄N₂O₅	详情	详情
(XI)	27700	methyl (E,4S)-4,8-diamino-8-oxo-2-octenoate		C₉H₁₆N₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVIII)

The tripeptide benzyl ester precursor (IV) is prepared by the following procedure. Condensation of N-Boc-L-leucine (X) with L-phenylalanine benzyl ester (XVIII) in the presence of DIEA, HOBt and PyBOP in acetonitrile gives the protected dipeptide (XIX), which upon deprotection by means of TFA in CH2Cl2 yields dipeptide (XX). Without isolation, intermediate (XX) is then condensed with N-Boc-L-homophenylalanine (XIV) in the presence of DEEA (diethyl-aminoethanol), HOBt and PyBOP in acetonitrile to provide protected tripeptide (XXI) , which is finally N-deprotected by means of TFA in CH2Cl2 .

参考文献中间体

合成目标

【1】 Smyth, M.S., Laidig, G.J. (Proteolix, Inc.). Compounds for proteasome enzyme inhibition. CA 2589765, EP 1781688, JP 2008509166, US 2009131421, WO 2006017842.
【2】 Smyth, M.S., Laidig, G.J., Borchardt, R.T. et al. (Proteolix, Inc.). Compounds for proteasome enzyme inhibition. EP 1745064, JP 2008501637, US 2005245435, US 2008200398, US 7232818, WO 2005105827.
【3】 Smyth, M.S., Laidig, G.J. (Proteolix, Inc.). Compounds for enzyme inhibition. US 2006030533, US 7417042.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	69393	(R)-benzyl 2-((S)-2-((R)-2-amino-4-phenylbutanamido)-4-methylpentanamido)-3-phenylpropanoate 2,2,2-trifluoroacetate		C₃₂H₃₉N₃O₄.C₂HF₃O₂	详情	详情
(X)	23663	(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine		C₁₁H₂₁NO₄	详情	详情
(XIV)	12874	(2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine	13734-34-4	C₁₄H₁₉NO₄	详情	详情
(XVIII)	27693	benzyl (2S)-2-amino-3-phenylpropanoate；L-phenylalanine benzyl ester		C₁₆H₁₇NO₂	详情	详情
(XIX)	69402	(R)-benzyl 2-((S)-2-((tert-butoxycarbonyl)amino)-4-methylpentanamido)-3-phenylpropanoate		C₂₇H₃₆N₂O₅	详情	详情
(XX)	69403	(R)-benzyl 2-((S)-2-amino-4-methylpentanamido)-3-phenylpropanoate 2,2,2-trifluoroacetate		C₂₂H₂₈N₂O₃.C₂HF₃O₂	详情	详情
(XXI)	69404	(6S,9S,12R)-benzyl 12-benzyl-9-isobutyl-2,2-dimethyl-4,7,10-trioxo-6-phenethyl-3-oxa-5,8,11-triazatridecan-13-oate		C₃₇H₄₇N₃O₆	详情	详情

Extended Information