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【结 构 式】 
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【分子编号】68328 【品名】methyl 4-[(dimethylamino)(imino)methyl]benzoate;methyl 4-(N,N-dimethylcarbamimidoyl)benzoate 【CA登记号】 |
【 分 子 式 】C11H14N2O2 【 分 子 量 】206.24444 【元素组成】C 64.06% H 6.84% N 13.58% O 15.51% |
合成路线1
该中间体在本合成路线中的序号：(XIa)The 4-amidinobenzoic acid intermediate (VII) is prepared by esterification of 4-cyanobenzoic acid (VIII) with MeOH in the presence of H2SO4 at reflux to give methyl 4-cyanobenzoate (IXa), which is then subjected to Pinner reaction with EtOH in the presence of HCl to yield methyl 4-[ethoxy(imino)methyl]benzoate (X). Without isolation, imidate (X) reacts with dimethylamine hydrochloride in refluxing EtOH to provide methyl 4-[(dimethylamino)(imino)methyl]benzoate (XIa). The analogous ethyl ester (XIb) can be alternatively prepared by reaction of ethyl 4-cyanobenzoate (IXb) with Me2NLi (generated from Me2NH and HexLi) in THF. Finally, either methyl (XIa) or ethyl (XIb) esters are hydrolyzed with LiOH in H2O/THF, and then acidified with HCl .
| 【1】 Pandey, A., Leitao, E.P.T., Rato, J., Song, Z.J. (Millennium Pharmaceuticals, Inc.; Merck & Co., Inc.). Methods of synthesizing factor Xa inhibitors. EP 2513058, US 201131927, WO 201108419. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IXa) | 10169 | methyl 4-cyanobenzoate；4-Cyanobenzoic acid methyl ester | 1129-35-7 | C9H7NO2 | 详情 | 详情 |
| (IXb) | 68326 | ethyl 4-cyanobenzoate | C10H9NO2 | 详情 | 详情 | |
| (XIa) | 68328 | methyl 4-[(dimethylamino)(imino)methyl]benzoate;methyl 4-(N,N-dimethylcarbamimidoyl)benzoate | C11H14N2O2 | 详情 | 详情 | |
| (XIb) | 68329 | ethyl 4-(N,N-dimethylcarbamimidoyl)benzoate | C12H16N2O2 | 详情 | 详情 | |
| (VII) | 68325 | 4-(N,N-dimethylcarbamimidoyl)benzoic acid hydrochloride | C10H12N2O2.HCl | 详情 | 详情 | |
| (VIII) | 36897 | 4-cyanobenzoic acid；4-Carboxybenzonitrile;p-Carboxybenzonitrile | 619-65-8 | C8H5NO2 | 详情 | 详情 |
| (X) | 68327 | methyl 4-[ethoxy(imino)methyl]benzoate | C11H13NO3 | 详情 | 详情 |