methyl (2S)-2-amino-4-phenylbutanoate -Drug Synthesis Database

【结构式】

【分子编号】24390

【品名】methyl (2S)-2-amino-4-phenylbutanoate

【CA登记号】

【分子式】C₁₁H₁₅NO₂

【分子量】193.24564

【元素组成】C 68.37% H 7.82% N 7.25% O 16.56%

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：(VIII)

The sodium salt of L-phenylalanine (I) was condensed with pivalaldehyde (II) in boiling pentane to afford imine (III). Subsequent reaction of (III) with benzyl chloroformate generated oxazolidinone (IV) as a 9:1 mixture of diastereoisomers, which were separated chromatographically. The required cis compound was treated with allyl bromide (V) in the presence of potassium hexamethyldisilazide in THF at -78 C to provide (VI) as the major isomer. Aldehyde (VII) was then obtained by ozonolysis of (VI) at -78 C. Reductive amination of (VII) with L-homophenylalanine methyl ester (VIII) using NaBH3CN yielded the corresponding amine (IX) which, upon heating in toluene in the presence of 1-hydroxybenzotriazole, afforded pyrrolidinone (X). Reduction of the ester function of (X) with Ca(BH4)2 gave alcohol (XI), which was finally oxidized under Swern conditions to the target aldehyde.

参考文献中间体

合成目标

【1】 Scheidt, K.A.; Roush, W.R.; McKerrow, J.H.; Selzer, P.M.; Hansell, E.; Rosenthal, P.J.; Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg Med Chem 1998, 6, 12, 2477.

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)	19797	Trimethylacetaldehyde; pivalaldehyde; 2,2-Dimethylpropionaldehyde; 2,2-Dimethylpropanal	630-19-3	C₅H₁₀O	详情	详情
(III)	24385	sodium (2S)-2-[[(E)-2,2-dimethylpropylidene]amino]-3-phenylpropanoate		C₁₄H₁₈NNaO₂	详情	详情
(IV)	24386	benzyl (4S)-4-benzyl-2-(tert-butyl)-5-oxo-1,3-oxazolidine-3-carboxylate		C₂₂H₂₅NO₄	详情	详情
(V)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(VI)	24388	benzyl (2S,4S)-4-allyl-4-benzyl-2-(tert-butyl)-5-oxo-1,3-oxazolidine-3-carboxylate		C₂₅H₂₉NO₄	详情	详情
(VII)	24389	benzyl (2S,4R)-4-benzyl-2-(tert-butyl)-5-oxo-4-(2-oxoethyl)-1,3-oxazolidine-3-carboxylate		C₂₄H₂₇NO₅	详情	详情
(VIII)	24390	methyl (2S)-2-amino-4-phenylbutanoate		C₁₁H₁₅NO₂	详情	详情
(IX)	24391	benzyl (2S,4R)-4-benzyl-2-(tert-butyl)-4-(2-[[(1S)-1-(methoxycarbonyl)-3-phenylpropyl]amino]ethyl)-5-oxo-1,3-oxazolidine-3-carboxylate		C₃₅H₄₂N₂O₆	详情	详情
(X)	24392	methyl (2S)-2-((3R)-3-benzyl-3-[[(benzyloxy)carbonyl]amino]-2-oxopyrrolidinyl)-4-phenylbutanoate		C₃₀H₃₂N₂O₅	详情	详情
(XI)	24393	benzyl (3R)-3-benzyl-1-[(1S)-1-(hydroxymethyl)-3-phenylpropyl]-2-oxopyrrolidinylcarbamate		C₂₉H₃₂N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The sodium salt of L-phenylalanine (I) was condensed with pivalaldehyde (II) in boiling pentane to afford imine (III). Subsequent reaction of (III) with benzyl chloroformate generated oxazolidinone (IV) as a 9:1 mixture of diastereoisomers, which were separated chromatographically. The required cis compound was treated with allyl bromide (V) in the presence of potassium hexamethyldisilazide in THF at -78 C to provide (VI) as the major isomer. Aldehyde (VII) was then obtained by ozonolysis of (VI) at -78 C. Reductive amination of (VII) with L-homophenylalanine methyl ester (VIII) using NaBH3CN yielded the corresponding amine (IX) which, upon heating in toluene in the presence of 1-hydroxybenzotriazole, afforded pyrrolidinone (X). The carbobenzoxy group of (X) was then removed by hydrogenolysis over Pd/C, and the resulting amine was acylated with benzenesulfonyl chloride to produce sulfonamide (XI). Finally, the target aldehyde was obtained by the sequence of ester reduction of (XI) with Ca(BH4)2, followed by Swern oxidation of the resulting alcohol.

参考文献中间体

合成目标

【1】 Scheidt, K.A.; Roush, W.R.; McKerrow, J.H.; Selzer, P.M.; Hansell, E.; Rosenthal, P.J.; Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg Med Chem 1998, 6, 12, 2477.

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)	19797	Trimethylacetaldehyde; pivalaldehyde; 2,2-Dimethylpropionaldehyde; 2,2-Dimethylpropanal	630-19-3	C₅H₁₀O	详情	详情
(III)	24385	sodium (2S)-2-[[(E)-2,2-dimethylpropylidene]amino]-3-phenylpropanoate		C₁₄H₁₈NNaO₂	详情	详情
(IV)	24386	benzyl (4S)-4-benzyl-2-(tert-butyl)-5-oxo-1,3-oxazolidine-3-carboxylate		C₂₂H₂₅NO₄	详情	详情
(V)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(VI)	24388	benzyl (2S,4S)-4-allyl-4-benzyl-2-(tert-butyl)-5-oxo-1,3-oxazolidine-3-carboxylate		C₂₅H₂₉NO₄	详情	详情
(VII)	24389	benzyl (2S,4R)-4-benzyl-2-(tert-butyl)-5-oxo-4-(2-oxoethyl)-1,3-oxazolidine-3-carboxylate		C₂₄H₂₇NO₅	详情	详情
(VIII)	24390	methyl (2S)-2-amino-4-phenylbutanoate		C₁₁H₁₅NO₂	详情	详情
(IX)	24391	benzyl (2S,4R)-4-benzyl-2-(tert-butyl)-4-(2-[[(1S)-1-(methoxycarbonyl)-3-phenylpropyl]amino]ethyl)-5-oxo-1,3-oxazolidine-3-carboxylate		C₃₅H₄₂N₂O₆	详情	详情
(X)	24392	methyl (2S)-2-((3R)-3-benzyl-3-[[(benzyloxy)carbonyl]amino]-2-oxopyrrolidinyl)-4-phenylbutanoate		C₃₀H₃₂N₂O₅	详情	详情
(XI)	24394	methyl (2S)-2-[(3R)-3-benzyl-2-oxo-3-[(phenylsulfonyl)amino]pyrrolidinyl]-4-phenylbutanoate		C₂₈H₃₀N₂O₅S	详情	详情

Extended Information