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【结 构 式】 
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【药物名称】 【化学名称】4-[1-(4-Amino-6,7-dimethoxyquinazolin-2-yl)piperidin-4-ylamino]benzoic acid 【CA登记号】 【 分 子 式 】C22H25N5O4 【 分 子 量 】423.47565 |
【开发单位】Isis Pharmaceuticals (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY |
合成路线1
Palladium-catalyzed coupling of 4-amino-1-benzylpiperidine (I) with tert-butyl 4-bromobenzoate (II) afforded the anilinopiperidine derivative (III). Removal of the benzyl protecting group of (III) to give (IV) was achieved by transfer hydrogenolysis in the presence of ammonium formate and Pd/C. Piperidine (IV) was then coupled with 4-amino-2-chloro-6,7-dimethoxyquinazoline (V) in hot isoamyl alcohol yielding piperidino quinazoline (VI). The title carboxylic acid was finally obtained by acidic deprotection of tert-butyl ester of (VI).
| 【1】 Casper, M.D.; Kung, P.-P.; Cook, K.L.; et al.; Structure-activity relationships of novel 2-substituted quinazoline antibacterial agents. J Med Chem 1999, 42, 22, 4705. |
| 【2】 Guinosso, C.J.; Cook, P.D.; Kung, P.-P. (Isis Pharmaceuticals, Inc.); Antibacterial quinazoline cpds.. US 6156758 . |
| 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) | 34808 | 1-Benzyl-4-piperidinylamine; 1-Benzyl-4-piperidinamine; 4-Amino-1-benzylpiperidine | 50541-93-0 | C12H18N2 | 详情 | 详情 |
| (II) | 14286 | tert-butyl 4-bromobenzoate | C11H13BrO2 | 详情 | 详情 | |
| (III) | 40527 | tert-butyl 4-[(1-benzyl-4-piperidinyl)amino]benzoate | C23H30N2O2 | 详情 | 详情 | |
| (IV) | 40528 | tert-butyl 4-(4-piperidinylamino)benzoate | C16H24N2O2 | 详情 | 详情 | |
| (V) | 10443 | 2-Chloro-6,7-dimethoxy-4-quinazolinamine; 4-Amino-2-chloro-6,7-dimethoxyquinazoline; 2-Chloro-6,7-dimethoxy-4-quinazolinylamine | 23680-84-4 | C10H10ClN3O2 | 详情 | 详情 |
| (VI) | 40529 | tert-butyl 4-[[1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]amino]benzoate | C26H33N5O4 | 详情 | 详情 |