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【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

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.

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.

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