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【结 构 式】 
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【分子编号】24280 【品名】N-[3-(methylamino)propyl]tetrahydro-2-furancarboxamide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;2-Furancarboxamide,tetrahydro-N-[3-(methylamino)propyl]- 【CA登记号】81403-67-0 |
【 分 子 式 】C9H18N2O2 【 分 子 量 】186.2542 【元素组成】C 58.04% H 9.74% N 15.04% O 17.18% |
合成路线1
该中间体在本合成路线中的序号：(VI)Title compound can be prepared as follows: 1) 6,7-Dimethoxyquinazolin-2,4-dione (I) is converted to 2,4-dichloro 6,7-dimethoxyquinazoline (II), followed by selective displacement of the 4-chloro group with ammonia to give 4-amino-2-chloro-6,7-dimethoxyquinazoline (III). 2) 3-(Methylamino)propanenitrile (IV) is reacted with the mixed anhydride obtained from tetrahydrofuran-2-carboxylic acid and ethyl chloroformate to form the amide (V), which on hydrogenation over rhodium at 80 C in the presence of ammonia affords the required secondary amine (VI) via rearrangement of the initially formed primary amine (VII). Condensation of amine (VI) with 4-amino-2-chloro-6,7-dimethoxyquinazoline (III) in refluxing amyl alcohol gives alfuzosin hydrochloride.
| 【1】 Binet, J.L.; Manoury, P.M.; Dumas, A.P.; Lefevre-Borg, F.; Cavero, I.; Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives. J Med Chem 1986, 29, 19-25. |
| 【2】 Cazor, J.L.; Borg, F.; Dimsdale, M.; Alfuzosin hydrochloride. Drugs Fut 1986, 11, 10, 821. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 62978 | C8H12O5 | 详情 | 详情 | |||
| (I) | 24275 | 6,7-Dimethoxy-2,4(1H,3H)-quinazolinedione; 6,7-Dimethoxyquinazoline-2,4-dione | 28888-44-0 | C10H10N2O4 | 详情 | 详情 |
| (II) | 24276 | 2,4-dichloro-6-methoxy-7-quinazolinyl methyl ether | 27631-29-4 | C10H8Cl2N2O2 | 详情 | 详情 |
| (III) | 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 |
| (IV) | 24278 | 3-(methylamino)propanenitrile | 693-05-0 | C4H8N2 | 详情 | 详情 |
| (V) | 24279 | N-(2-cyanoethyl)-N-methyltetrahydro-2-furancarboxamide | C9H14N2O2 | 详情 | 详情 | |
| (VI) | 24280 | N-[3-(methylamino)propyl]tetrahydro-2-furancarboxamide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;2-Furancarboxamide,tetrahydro-N-[3-(methylamino)propyl]- | 81403-67-0 | C9H18N2O2 | 详情 | 详情 |
| (VII) | 24281 | N-(3-aminopropyl)-N-methyltetrahydro-2-furancarboxamide | C9H18N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIII)
| 【1】 Anumula RR.Alla S,Gilla G.et al.2007.Process for preoration alfuzosin Via esterification oftetra-hydro-2-furoic acid followed by coupling with N-methrd-l,3-propanediamine, US 2007066824 |
| 【2】 Hu GY，Xiang HL，Xu LML 2007．PrepantionofaKuzosin发明专利申请公开说明书，CN 1935806 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 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 |
| (X) | 66070 | N-(3-((4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino)propyl)tetrahydrofuran-2-carboxamide | C19H27N5O4 | 详情 | 详情 | |
| (XXIII) | 24280 | N-[3-(methylamino)propyl]tetrahydro-2-furancarboxamide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;2-Furancarboxamide,tetrahydro-N-[3-(methylamino)propyl]- | 81403-67-0 | C9H18N2O2 | 详情 | 详情 |