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【结 构 式】 
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【药物名称】 【化学名称】N-(4-Bromophenyl)-4-(6,7-dimethoxy-4-quinazolinyl)piperazine-1-carboxamide 【CA登记号】205254-79-1 【 分 子 式 】C21H22BrN5O3 【 分 子 量 】472.34519 |
【开发单位】Kyowa Hakko (Originator), Millennium (Codevelopment) 【药理作用】Atherosclerosis Therapy, CARDIOVASCULAR DRUGS, ONCOLYTIC DRUGS, Restenosis Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, PDGFR Inhibitors |
合成路线1
The title urea derivative was synthesized by condensation of 6,7-dimethoxy-4-piperazinylquinazoline (I) with 4-bromophenyl isocyanate (II) in refluxing ethanol.
| 【1】 Matsuno, K.; Ichimura, M.; Nakajima, T.; Tahara, K.; Fujiwara, S.; Kase, H.; Ushiki, J.; Giese, N.A.; Pandey, A.; Scarborough, R.M.; Lokker, N.A.; Yu, J.C.; Irie, J.; Tsukuda, E.; Ide, S.-i; Oda, S.; Nomoto, Y.; Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 1. Synthesis, structure-activity relationship, and biological effects of a new class of quinazoline derivatives. J Med Chem 2002, 45, 14, 3057. |
| 【2】 Matsuno, K.; Ichimura, M.; Nomoto, Y.; Fujiwara, S.; Ide, S.; Tsukuda, E.; Irie, J.; Oda, S. (Kyowa Hakko Kogyo Co., Ltd.); Nitrogenous heterocyclic cpds. EP 0882717; WO 9814431 . |
合成路线2
The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-bromophenylamine (II) by means of CDI or triphosgene gives the target piperazine-1-carboxamide. Alternatively, the reaction of 4-bromophenylamine (II) with 4-nitrophenyl chloroformate (III) by means of TEA gives the carbamate (IV), which is finally condensed with the quinazoline (I) in hot NMP to yield the target piperazine-1-carboxamide.
| 【1】 Matsuno, K.; Ichimura, M.; Nakajima, T.; Tahara, K.; Fujiwara, S.; Kase, H.; Ushiki, J.; Giese, N.A.; Pandey, A.; Scarborough, R.M.; Lokker, N.A.; Yu, J.C.; Irie, J.; Tsukuda, E.; Ide, S.-i; Oda, S.; Nomoto, Y.; Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 1. Synthesis, structure-activity relationship, and biological effects of a new class of quinazoline derivatives. J Med Chem 2002, 45, 14, 3057. |
| 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) | 41610 | 6,7-dimethoxy-4-(1-piperazinyl)quinazoline; 6-methoxy-4-(1-piperazinyl)-7-quinazolinyl methyl ether | C14H18N4O2 | 详情 | 详情 | |
| (II) | 22351 | ethyl 3-([2-amino-5-[(4-cyanobenzoyl)amino]benzoyl]amino)propanoate | C20H20N4O4 | 详情 | 详情 | |
| (III) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
| (IV) | 63170 | 4-nitrophenyl 4-bromophenylcarbamate | C13H9BrN2O4 | 详情 | 详情 |