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【结 构 式】 
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【药物名称】CL-387785 【化学名称】N-[4-(3-Bromophenylamino)quinazolin-6-yl]-2-butynamide 【CA登记号】 【 分 子 式 】C18H13BrN4O 【 分 子 量 】381.23451 |
【开发单位】American Home Products 【药理作用】ONCOLYTIC DRUGS, INHIBITORS OF SIGNAL TRANSDUCTION PATHWAYS |
合成路线1
The reaction of 2-amino-5-nitrobenzoic acid (I) with N,N-dimethylformamide dimethylacetal (II) by heating at 100 C gives the formamidine (III), which is cyclized with 3-bromoaniline (IV) in refluxing acetic acid yielding 4-(3-bromophenyl)-6-nitroquinazoline (V). The reduction of (V) with Fe and acetic acid affords the amine (VI), which is finally acylated with 2-butynoic acid by means of isobutyl chloroformate and N-methylmorpholine in THF.
| 【1】 Wissner, A.; Johnson, B.D.; Floyd, M.B. Jr.; Kitchen, D.B. (American Cyanamid Co.); 4-Aminoquinazoline EGFR inhibitors. EP 0787722; US 5760041 . |
| 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) | 23218 | 2-amino-5-nitrobenzonitrile | 17420-30-3 | C7H5N3O2 | 详情 | 详情 |
| (II) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (III) | 23219 | N'-(2-cyano-4-nitrophenyl)-N,N-dimethyliminoformamide | C10H10N4O2 | 详情 | 详情 | |
| (IV) | 19136 | 3-bromoaniline; 3-bromophenylamine; 3-bromobenzenamine | 591-19-5 | C6H6BrN | 详情 | 详情 |
| (V) | 23221 | N-(3-bromophenyl)-N-(6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-6-nitro-4-quinazolinamine | C14H9BrN4O2 | 详情 | 详情 | |
| (VI) | 23222 | N(4)-(3-bromophenyl)-4,6-quinazolinediamine; N-(6-amino-4-quinazolinyl)-N-(3-bromophenyl)amine | C14H11BrN4 | 详情 | 详情 | |
| (VII) | 10938 | 2-Butynoic acid | 590-93-2 | C4H4O2 | 详情 | 详情 |
Extended Information