|
【结 构 式】 
|
【分子编号】19559 【品名】4-Chloroisatoic anhydride; 7-chloro-2H-3,1-benzoxazine-2,4(1H)-dione 【CA登记号】 |
【 分 子 式 】C8H4ClNO3 【 分 子 量 】197.5774 【元素组成】C 48.63% H 2.04% Cl 17.94% N 7.09% O 24.29% |
合成路线1
该中间体在本合成路线中的序号：(II)1) The cyclization of 2-(benzyloxycarbonylamino)-4-chlorobenzoic acid (I) by means of PBr3 in refluxing ethyl ether gives 7-chloro-2H-3,1-benzoxazine-2,4(1H)-dione (II), which is condensed with 4-bromo-2-fluorobenzylamine (III) in refluxing THF yielding 2-amino-N-(4-bromo-2-fluorobenzyl)-4-chloro-benzamide (IV). The cyclization of (IV) with carbonyldiimidazole (CDI) in refluxing dioxane affords 3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydroquinazoline-2,4-dione (V), which is alkylated with ethyl bromoacetate (VI) by means of NaH in DMF to give ethyl 3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-1-acetate (VII). Finally, this compound is hydrolyzed with NaOH in refluxing methanol.
| 【1】 Hashimoto, M.; Oku, T.; Ito, Y.; Namiki, T.; Sawada, K.; Kasahara, C.; Baba, Y. (Fujisawa Pharmaceutical Co., Ltd.); New quinazoline derivs., process for their production and pharmaceutical compsns. comprising them. EP 0218999; JP 1987096476; JP 1989125322; JP 1989131164; US 4734419; US 4883800 . |
| 【2】 Prous, J.; Castaner, J.; FR-74366. Drugs Fut 1989, 14, 1, 26. |
| 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) | 19558 | 2-[[(benzyloxy)carbonyl]amino]-4-chlorobenzoic acid | C15H12ClNO4 | 详情 | 详情 | |
| (II) | 19559 | 4-Chloroisatoic anhydride; 7-chloro-2H-3,1-benzoxazine-2,4(1H)-dione | C8H4ClNO3 | 详情 | 详情 | |
| (III) | 19560 | (4-bromo-2-fluorophenyl)methanamine; 4-bromo-2-fluorobenzylamine | 112734-22-2 | C7H7BrFN | 详情 | 详情 |
| (IV) | 19561 | 2-amino-N-(4-bromo-2-fluorobenzyl)-4-chlorobenzamide | C14H11BrClFN2O | 详情 | 详情 | |
| (V) | 19562 | 3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4(1H,3H)-quinazolinedione | C15H9BrClFN2O2 | 详情 | 详情 | |
| (VI) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (VII) | 19564 | ethyl 2-[3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-3,4-dihydro-1(2H)-quinazolinyl]acetate | C19H15BrClFN2O4 | 详情 | 详情 |