【结 构 式】 |
【药物名称】 【化学名称】3-[5-(6-Chloropyridin-3-ylcarbonyl)-1-methyl-1H-pyrrol-2-yl]-N-[2,4-dichloro-3-(2-methylquinolin-8-yloxymethyl)phenyl]-N-methylpropionamide 【CA登记号】 【 分 子 式 】C32H27Cl3N4O3 【 分 子 量 】621.95599 |
【开发单位】Johnson & Johnson (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Bradykinin B2 Antagonists |
合成路线1
Wittig reaction of 1-methylpyrrole-2-carboxaldehyde (I) with (ethoxycarbonylmethylene)triphenylphosphorane furnishes the pyrrolylacrylate ester (II), which is subsequently hydrogenated over Pd/C to the pyrrolylpropionate (III). Friedel-Crafts acylation of pyrrole (III) with 6-chloronicotinoyl chloride (IV) gives rise to the pyrrolyl ketone (V). After alkaline hydrolysis of the ethyl ester group of (V), the resultant carboxylic acid (VI) is converted into the corresponding acid chloride (VII) employing oxalyl chloride and DMF. Finally, coupling of acid chloride (VII) with the known aniline derivative (VIII) leads to the desired amide.
【1】 Youngman, M.A.; Carson, J.R.; Lee, J.S.; Dax, S.L.; Zhang, S.-P.; Colburn, R.W.; Stone, D.J.; Codd, E.E.; Jetter, M.C.; Synthesis and structure-activity relationships of aroylpyrrole alkylamide bradykinin (B2) antagonists. Bioorg Med Chem Lett 2003, 13, 7, 1341. |
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) | 64337 | 1-methyl-1H-pyrrole-2-carbaldehyde | C6H7NO | 详情 | 详情 | |
(II) | 64338 | ethyl 3-(1-methyl-1H-pyrrol-2-yl)-2-propenoate | C10H13NO2 | 详情 | 详情 | |
(III) | 64339 | ethyl 3-(1-methyl-1H-pyrrol-2-yl)propanoate | C10H15NO2 | 详情 | 详情 | |
(IV) | 30256 | 6-chloronicotinoyl chloride | 58757-38-3 | C6H3Cl2NO | 详情 | 详情 |
(V) | 64340 | ethyl 3-{5-[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-1H-pyrrol-2-yl}propanoate | C16H17ClN2O3 | 详情 | 详情 | |
(VI) | 64341 | 3-{5-[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-1H-pyrrol-2-yl}propanoic acid | C14H13ClN2O3 | 详情 | 详情 | |
(VII) | 64342 | 3-{5-[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-1H-pyrrol-2-yl}propanoyl chloride | C14H12Cl2N2O2 | 详情 | 详情 | |
(VIII) | 64343 | 2,4-dichloro-N-methyl-3-{[(2-methyl-8-quinolinyl)oxy]methyl}aniline; N-(2,4-dichloro-3-{[(2-methyl-8-quinolinyl)oxy]methyl}phenyl)-N-methylamine | C18H16Cl2N2O | 详情 | 详情 |