【结 构 式】 |
【药物名称】CGS-13928C 【化学名称】1-[N-[1(S)-(Ethoxycarbonyl)-3-phenyl-1S-propyl]alanyl]-2,3-dihydroindole-2(S)-carboxylic acid sodium salt 【CA登记号】 【 分 子 式 】C24H27N2NaO5 【 分 子 量 】446.48299 |
【开发单位】Novartis (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Angiotensin-I Converting Enzyme (ACE) Inhibitors |
合成路线1
The condensation of ethyl indoline-2-carboxylate (I) with N-benzyloxycarbonylalanine (II) by means of CH2Cl2 gives ethyl N-(benzyloxycarbonylalanyl)indoline-2-carboxylate (III), which is hydrolyzed partially with LiOH in DMF water yielding N-(benzyloxycarbonylalanyl)indoline-2-carboxylic acid (IV). Debenzylation of (IV) by hydrogenation with H2 over Pd/C in aqueous ethanol affords N-alanylindoline-2-carboxylic acid, which is finally reductocondensed with ethyl 2-oxo-3-phenylbutyrate (VI) by means of NaOH and sodium cyanoborohydride or H2 and RaNi in ethanol.
【1】 Renfroe, H.B.; Stanton, J.L.; Sele, A. (Novartis AG); 1-Carboxy-azaalkyl-indolin-2-carboxylic acids, process for preparing them, pharmaceutical compositions containing them and their therapeutical use. DD 201888; EP 0051301; GB 2086390 . |
【2】 Serradell, M.N.; Castaner, J.; CGS-13928C. Drugs Fut 1985, 10, 3, 190. |
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) | 29042 | ethyl (2S)-1-methyl-2,3-dihydro-1H-indole-2-carboxylate | C12H15NO2 | 详情 | 详情 | |
(II) | 61209 | CBZ-L-Alanine; (2S)-2-[[(Benzyloxy)carbonyl]amino]propionic acid; N-((Phenylmethoxy)carbonyl)-alanine; Carbobenzyloxy-L-alanine | C11H13NO4 | 详情 | 详情 | |
(III) | 29043 | ethyl (2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-2,3-dihydro-1H-indole-2-carboxylate | C22H24N2O5 | 详情 | 详情 | |
(IV) | 29044 | (2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-2,3-dihydro-1H-indole-2-carboxylic acid | C20H20N2O5 | 详情 | 详情 | |
(V) | 29045 | (2S)-1-[(2S)-2-aminopropanoyl]-2,3-dihydro-1H-indole-2-carboxylic acid | C12H14N2O3 | 详情 | 详情 | |
(VI) | 20896 | Ethyl 2-oxo-4-phenylbutanoate; 2-Oxo-4-phenylbutyric acid ethyl ester | 64920-29-2 | C12H14O3 | 详情 | 详情 |