ethyl 2-[[(1S)-2-(tert-butoxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate -Drug Synthesis Database

【结构式】

【分子编号】31121

【品名】ethyl 2-[[(1S)-2-(tert-butoxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate

【CA登记号】

【分子式】C₁₉H₂₉NO₄

【分子量】335.4436

【元素组成】C 68.03% H 8.71% N 4.18% O 19.08%

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)

The condensation of alanine tert-butyl ester (I) with ethyl 2-bromo-4-phenylbutanoate (II) by means of triethylamine in hot DMF gives ethyl 2-[[1-(tert-butoxycarbonyl)ethyl]amino]-4-phenylbutanoate (III), which is partially hydrolyzed with trifluoroacetic acid yielding ethyl 2-[[1-carboxyethyl]amino]-4-phenylbutanoate (IV). The condensation of (IV) with benzyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate (V) [prepared from the corresponding acid (VI) and benzyl alcohol (A) by means of polyphosphoric acid] by means of triethylamine and 1-hydroxybenzotriazole affords benzyl 2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (VII), which is finally debenzylated by hydrogenolysis with H2 over Pd/C in THF.

参考文献中间体

合成目标

【1】 Hoefle, M.L.; Klutchko, S. (Pfizer Inc.); Substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids. DD 201787; EP 0049605; EP 0096157; US 4344949 .
【2】 Castaner, J.; Serradell, M.N.; Blancafort, P.; CI-906. Drugs Fut 1983, 8, 12, 1014.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	18710	Benzyl alcohol; Phenylmethanol	100-51-6	C₇H₈O	详情	详情
(I)	29385	tert-butyl (2S)-2-aminopropanoate		C₇H₁₅NO₂	详情	详情
(II)	20810	ethyl 2-bromo-4-phenylbutanoate		C₁₂H₁₅BrO₂	详情	详情
(III)	31121	ethyl 2-[[(1S)-2-(tert-butoxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate		C₁₉H₂₉NO₄	详情	详情
(IV)	31124	(2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid		C₁₅H₂₁NO₄	详情	详情
(V)	31122	benzyl 1,2,3,4-tetrahydro-3-isoquinolinecarboxylate		C₁₇H₁₇NO₂	详情	详情
(VI)	13953	(3S)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid; (S)-(-)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid	74163-81-8	C₁₀H₁₁NO₂	详情	详情
(VII)	31123	benzyl 2-((2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate		C₃₂H₃₆N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The condensation of alanine tert-butyl ester (I) with ethyl 2-bromo-4-phenylbutanoate (II) by means of triethylamine in hot DMF gives ethyl 2-[[1-(tert-butoxycarbonyl)ethyl]amino]-4-phenylbutanoate (III), which is partially hydrolyzed with trifluoroacetic acid yielding ethyl 2-[[1-carboxyethyl]amino]-4-phenylbutanoate (IV). The condensation of (IV) with tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (VIII) [prepared from the corresponding acid (VI) and isobutylene (B) by means of H2SO4] as before gives tert-butyl-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (IX), which is finally hydrolyzed partially by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Hoefle, M.L.; Klutchko, S. (Pfizer Inc.); Substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids. DD 201787; EP 0049605; EP 0096157; US 4344949 .
【2】 Castaner, J.; Serradell, M.N.; Blancafort, P.; CI-906. Drugs Fut 1983, 8, 12, 1014.

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)	15926	2-methyl-1-propene; isobutylene	115-11-7	C₄H₈	详情	详情
(I)	29385	tert-butyl (2S)-2-aminopropanoate		C₇H₁₅NO₂	详情	详情
(II)	20810	ethyl 2-bromo-4-phenylbutanoate		C₁₂H₁₅BrO₂	详情	详情
(III)	31121	ethyl 2-[[(1S)-2-(tert-butoxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate		C₁₉H₂₉NO₄	详情	详情
(IV)	31124	(2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid		C₁₅H₂₁NO₄	详情	详情
(VI)	13953	(3S)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid; (S)-(-)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid	74163-81-8	C₁₀H₁₁NO₂	详情	详情
(VIII)	31125	tert-butyl 1,2,3,4-tetrahydro-3-isoquinolinecarboxylate		C₁₄H₁₉NO₂	详情	详情
(IX)	31126	tert-butyl 2-((2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate		C₂₉H₃₈N₂O₅	详情	详情

Extended Information