2-pyridinylmethyl 2-([[(1S,3S,4S)-4-amino-1-benzyl-3-hydroxy-5-phenylpentyl]amino]carbonyl)phenylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】41852

【品名】2-pyridinylmethyl 2-([[(1S,3S,4S)-4-amino-1-benzyl-3-hydroxy-5-phenylpentyl]amino]carbonyl)phenylcarbamate

【CA登记号】

【分子式】C₃₂H₃₄N₄O₄

【分子量】538.64652

【元素组成】C 71.36% H 6.36% N 10.4% O 11.88%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VII)

The reaction of L-phenylalanine (I) with benzyl chloride and K2CO3 gives the tribenzylated compound (II), which is condensed with acetonitrile by means of NaNH2 yielding 4(S)-(dibenzylamino)-3-oxo-4-phenylbutyronitrile (III). The reaction of (III) with benzylmagnesium chloride in THF affords the unsaturated, partially protected diaminohexenone (IV), which is reduced with NaBH4 and NaBH3(OTf) to provide a mixture of diastereomeric diaminohexanones, from which the desired diastereomer (V) is isolated by crystallization. The acylation of the free amino group of (V) with acylated anthranilic acid (VI) by means of HOBT gives the expected amide (VII), which is debenzylated by treatment with Pd/C and ammonium formate yielding intermediate (VIII). Finally this compound is acylated with the activated N-succinylcarbamate (IX) to afford the desired target compound.

参考文献中间体

合成目标

【1】 Stuk, T.L.; et al.; An efficient stereocontrolled strategy for the synthesis of hydroxyethylene dipeptide isosteres. J Org Chem 1994, 59, 15, 4040.
【2】 Randad, R.S.; Lubkowska, L.; Eissenstat, M.A.; Gulnik, S.V.; Yu, B.; Bhat, T.N.; Clanton, D.J.; House, T.; Stinson, S.F.; Erickson, J.W.; Unsymmetric nonpeptidic HIV protease inhibitors containing anthranilamide as a P2' ligand. Bioorg Med Chem Lett 1998, 8, 24, 3537.

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)	13952	(S)-(-)-Phenylalanine; L-Phenylalanine	63-91-2	C₉H₁₁NO₂	详情	详情
(II)	37670	benzyl (2S)-2-(dibenzylamino)-3-phenylpropanoate		C₃₀H₂₉NO₂	详情	详情
(III)	38263	(4S)-4-(dibenzylamino)-3-oxo-5-phenylpentanenitrile		C₂₅H₂₄N₂O	详情	详情
(IV)	37671	(2S,4E)-5-amino-2-(dibenzylamino)-1,6-diphenyl-4-hexen-3-one		C₃₂H₃₂N₂O	详情	详情
(V)	37672	(2S,3S,5S)-5-amino-2-(dibenzylamino)-1,6-diphenyl-3-hexanol		C₃₂H₃₆N₂O	详情	详情
(V)	41850	2-[[(2-pyridinylmethoxy)carbonyl]amino]benzoic acid		C₁₄H₁₂N₂O₄	详情	详情
(VI)	41851	2-pyridinylmethyl 2-([[(1S,3S,4S)-1-benzyl-4-(dibenzylamino)-3-hydroxy-5-phenylpentyl]amino]carbonyl)phenylcarbamate		C₄₆H₄₆N₄O₄	详情	详情
(VII)	41852	2-pyridinylmethyl 2-([[(1S,3S,4S)-4-amino-1-benzyl-3-hydroxy-5-phenylpentyl]amino]carbonyl)phenylcarbamate		C₃₂H₃₄N₄O₄	详情	详情
(VIII)	41853	1,3-thiazol-5-ylmethyl 2,5-dioxo-1-pyrrolidinecarboxylate		C₉H₈N₂O₄S	详情	详情

Extended Information