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【结 构 式】 
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【分子编号】49075 【品名】N-(2,2-diethoxyethyl)-4-fluorobenzenecarboximidamide 【CA登记号】 |
【 分 子 式 】C13H19FN2O2 【 分 子 量 】254.3045432 【元素组成】C 61.4% H 7.53% F 7.47% N 11.02% O 12.58% |
合成路线1
该中间体在本合成路线中的序号：(IV)The intermediate pyrimidineacetic acid (X) was prepared as follows. 4-Fluorobenzonitrile (I) was converted to the corresponding imidate (II) by treatment with ethanolic HCl. Reaction of imidate (II) with aminoacetaldehyde diethyl acetal (III) produced amidine (IV), which was condensed with diethyl ethoxymethylenemalonate (V) in boiling EtOH to furnish pyrimidinone (VI). Hydrolysis of the ethyl ester function of (VI) was carried out by treatment with LiI in hot pyridine. The resulting carboxylic acid (VII) was then subjected to a Curtius rearrangement with diphenylphosphoryl azide, and the intermediate isocyanate was subsequently condensed with benzyl alcohol, producing the benzyl carbamate (VIII). Acid hydrolysis of the diethyl acetal group of (VIII) gave aldehyde (IX), which was then oxidized to carboxylic acid (X) by using sodium chlorite.
| 【1】 Akahoshi, F.; Yoshimura, T.; Eda, M.; Ashimori, A.; Fukuyama, H.; Nakajima, M.; Imada, T.; Okunishi, H.; Miyazaki, M. (Welfide Corporation); Heterocyclic amide cpds. and medicinal use of the same. EP 0826671; US 5948785; WO 9633974 . |
| 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) | 14144 | 4-Fluorobenzonitrile | 1194-02-1 | C7H4FN | 详情 | 详情 |
| (II) | 49074 | ethyl 4-fluorobenzenecarboximidoate | C9H10FNO | 详情 | 详情 | |
| (III) | 10331 | 2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal | 645-36-3 | C6H15NO2 | 详情 | 详情 |
| (IV) | 49075 | N-(2,2-diethoxyethyl)-4-fluorobenzenecarboximidamide | C13H19FN2O2 | 详情 | 详情 | |
| (V) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (VI) | 49076 | ethyl 1-(2,2-diethoxyethyl)-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-5-pyrimidinecarboxylate | C19H23FN2O5 | 详情 | 详情 | |
| (VII) | 49077 | 1-(2,2-diethoxyethyl)-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-5-pyrimidinecarboxylic acid | C17H19FN2O5 | 详情 | 详情 | |
| (VIII) | 49078 | benzyl 1-(2,2-diethoxyethyl)-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-5-pyrimidinylcarbamate | C24H26FN3O5 | 详情 | 详情 | |
| (IX) | 49079 | benzyl 2-(4-fluorophenyl)-6-oxo-1-(2-oxoethyl)-1,6-dihydro-5-pyrimidinylcarbamate | C20H16FN3O4 | 详情 | 详情 | |
| (X) | 49080 | 2-[5-[[(benzyloxy)carbonyl]amino]-2-(4-fluorophenyl)-6-oxo-1(6H)-pyrimidinyl]acetic acid | C20H16FN3O5 | 详情 | 详情 |