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【结 构 式】 
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【分子编号】41610 【品名】6,7-dimethoxy-4-(1-piperazinyl)quinazoline; 6-methoxy-4-(1-piperazinyl)-7-quinazolinyl methyl ether 【CA登记号】 |
【 分 子 式 】C14H18N4O2 【 分 子 量 】274.32268 【元素组成】C 61.3% H 6.61% N 20.42% O 11.66% |
合成路线1
该中间体在本合成路线中的序号：(I)The title thiourea derivative was prepared by condensation of 6,7-dimethoxy-4-piperazinylquinazoline (I) with 1,3-benzodioxol-5-ylmethyl isothiocyanate (II) in refluxing ethanol.
| 【1】 Matsuno, K.; et al.; Potent and selective inhibitors of PDGF receptor phosphorylation. 2. Synthesis, structure activity relationship, improvement of aqueous solubility, and biological effects of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline deri. J Med Chem 2002, 45, 20, 4513. |
| 【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
该中间体在本合成路线中的序号：(I)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3
该中间体在本合成路线中的序号：(I)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 |
合成路线4
该中间体在本合成路线中的序号：(I)The target piperazine-1-carboxamide has been obtained by several different methods: 1.- The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-chlorophenyl isocyanate (II) in DMF gives the target compound. 2.- The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-chlorophenylamine (III) by means of CDI or triphosgene also gives the target piperazine-1-carboxamide. 3.- The reaction of 4-chlorophenylamine (III) with 4-nitrophenyl chloroformate (IV) by means of TEA gives the carbamate (V), 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) | 12035 | 4-chlorophenyl isocyanate; 1-Chloro-4-isocyanatobenzene; p-Chlorophenyl isocyanate | 104-12-1 | C7H4ClNO | 详情 | 详情 |
| (III) | 12034 | 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline | 106-47-8 | C6H6ClN | 详情 | 详情 |
| (IV) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
| (V) | 63171 | 4-nitrophenyl 4-chlorophenylcarbamate | C13H9ClN2O4 | 详情 | 详情 |