【结 构 式】 |
【分子编号】54740 【品名】ethyl 4-{[(3R)-1-(2-{(2R)-2-[2-(6-cyano-1-ethyl-1H-indol-2-yl)ethyl]pyrrolidinyl}-2-oxoethyl)-2-oxoazepanyl]amino}butanoate 【CA登记号】 |
【 分 子 式 】C31H43N5O4 【 分 子 量 】549.71372 【元素组成】C 67.73% H 7.88% N 12.74% O 11.64% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The reaction of perhydroazepinone (I) with ethyl 2-bromoacetate (II) by means of LiHMDS in THF, followed by hydrolysis with KOH in methanol/water, gives the perhydroazepinylacetic acid (III), which is condensed with the pyrrolidine derivative (IV) by means of HOBt, WSCl and DIEA in dichloromethane to yield the adduct (V). The cleavage of the carbamate group of (V) with TFA in dichloromethane affords the 3-aminoperhydroazepinone (VI), which is condensed with ethyl 4-bromobutyrate (VII) by means of DIEA in acetonitrile to provide the 4-aminobutyrate derivative (VIII). The reaction of the cyano group of (VIII) with HCl in ethanol, followed by amonolysis with NH3 in the same solvent, gives the carboxamidine derivative (IX), which is hydrolyzed with KOH in ethanol/water to yield the target butyric acid derivative.
【1】 Park, C.-H.; Koo, B.-A.; Nam, W.-H. (C & C Research Laboratories); Substd. aromatic amidine deriv. and medicinal compsn. comprising the same. WO 0055156 . |
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) | 54736 | 2,2-dimethyl-N-[(3R)-2-oxoazepanyl]propanamide | C11H20N2O2 | 详情 | 详情 | |
(II) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
(III) | 54737 | 2-{(3R)-3-[(2,2-dimethylpropanoyl)amino]-2-oxoazepanyl}acetic acid | C13H22N2O4 | 详情 | 详情 | |
(IV) | 50438 | 1-ethyl-2-[2-[(2S)pyrrolidinyl]ethyl]-1H-indole-6-carbonitrile | C17H21N3 | 详情 | 详情 | |
(V) | 54738 | N-[(3R)-1-(2-{(2R)-2-[2-(6-cyano-1-ethyl-1H-indol-2-yl)ethyl]pyrrolidinyl}-2-oxoethyl)-2-oxoazepanyl]-2,2-dimethylpropanamide | C30H41N5O3 | 详情 | 详情 | |
(VI) | 54739 | 2-[2-((2R)-1-{2-[(3R)-3-amino-2-oxoazepanyl]acetyl}pyrrolidinyl)ethyl]-1-ethyl-1H-indole-6-carbonitrile | C25H33N5O2 | 详情 | 详情 | |
(VII) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
(VIII) | 54740 | ethyl 4-{[(3R)-1-(2-{(2R)-2-[2-(6-cyano-1-ethyl-1H-indol-2-yl)ethyl]pyrrolidinyl}-2-oxoethyl)-2-oxoazepanyl]amino}butanoate | C31H43N5O4 | 详情 | 详情 | |
(IX) | 54741 | ethyl 4-[((3R)-1-{2-[(2R)-2-(2-{6-[amino(imino)methyl]-1-ethyl-1H-indol-2-yl}ethyl)pyrrolidinyl]-2-oxoethyl}-2-oxoazepanyl)amino]butanoate | C31H46N6O4 | 详情 | 详情 |