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【结 构 式】 
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【药物名称】FR-183998 【化学名称】N-(Diaminomethylene)-4-(2,5-dichlorothiophen-3-yl)-N'-[2-(dimethylamino)ethyl]isophthalamide dihydrochloride 【CA登记号】177733-06-1 【 分 子 式 】C17H21Cl4N5O2S 【 分 子 量 】501.26522 |
【开发单位】Fujisawa (Originator) 【药理作用】Angina pectoris, Treatment of, Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Na+/H+ Exchange (NHE) Inhibitors |
合成路线1
Mitsunobu coupling between boronic acid (I) and 3-bromo-2,5-dichlorothiophene (II) affords the thienyl isophthalate (III). Partial hydrolysis of diester (III) using methanolic KOH gives rise to mono-acid (IV), which is further condensed with N,N-dimethyl ethylenediamine (V) to provide the amide-ester (VI). Displacement of the methyl ester function of (VI) by guanidine (VII) then produces the target acyl guanidine, which is finally converted into the corresponding dihydrochloride salt.
| 【1】 Kuno, A.; Mizuno, H.; Yamasaki, K.; Inoue, Y. (Fujisawa Pharmaceutical Co., Ltd.); Benzoylguanidine derivs. as medicaments. JP 1998503770; WO 9604241 . |
| 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) | 58211 | 3,5-bis(methoxycarbonyl)phenylboronic acid | C10H11BO6 | 详情 | 详情 | |
| (II) | 58212 | 3-bromo-2,5-dichlorothiophene | 60404-18-4 | C4HBrCl2S | 详情 | 详情 |
| (III) | 58213 | dimethyl 5-(2,5-dichloro-3-thienyl)isophthalate | C14H10Cl2O4S | 详情 | 详情 | |
| (IV) | 58214 | 3-(2,5-dichloro-3-thienyl)-5-(methoxycarbonyl)benzoic acid | C13H8Cl2O4S | 详情 | 详情 | |
| (V) | 14881 | N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine | 108-00-9 | C4H12N2 | 详情 | 详情 |
| (VI) | 58215 | methyl 3-(2,5-dichloro-3-thienyl)-5-({[2-(dimethylamino)ethyl]amino}carbonyl)benzoate | C17H18Cl2N2O3S | 详情 | 详情 | |
| (VII) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |