|
【结 构 式】 
|
【药物名称】FR-177995 【化学名称】2,6-Dichloro-N-[1-[2-(4-morpholinyl)-2-oxoethyl]-2-(trifluoromethyl)-1H-benzimidazol-4-yl]benzamide 【CA登记号】189043-21-8 【 分 子 式 】C21H17Cl2F3N4O3 【 分 子 量 】501.29584 |
【开发单位】Fujisawa (Originator) 【药理作用】Bone Diseases, Treatment of, Bone Resorption Inhibitors, METABOLIC DRUGS, Treatment of Osteoporosis |
合成路线1
Condensation of 3-nitro-1,2-phenylenediamine (I) with trifluoroacetic acid provided benzimidazole (II). Reduction of the nitro group of (II) by means of hydrazine in the presence of FeCl3 and activated carbon gave amine (III), which was coupled with 2,6-dichlorobenzoyl chloride (IV) yielding amide (V). Alkylation of (V) with tert-butyl bromoacetate afforded benzimidazoleacetic acid tert-butyl ester (VI). After trifluoroacetic acid-promoted cleavage of the tert-butyl ester of (VI) the resulting carboxylic acid (VII) was coupled with morpholine (VIII) using EDC to furnish the title morpholide.
| 【1】 Oku, T.; Kawai, Y.; Yatabe, T.; Sato, S.; Yamazaki, H.; Kayakiri, N.; Yoshihara, K. (Fujisawa Pharmaceutical Co., Ltd.); Benzimidazole derivs. and their use in the prevention and/or the treatment of bone diseases. EP 0863881; JP 1999513364; WO 9710219 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 | |
| (I) | 38446 | 2-amino-3-nitrophenylamine; 3-nitro-1,2-benzenediamine | 3694-52-8 | C6H7N3O2 | 详情 | 详情 |
| (II) | 38447 | 4-nitro-2-(trifluoromethyl)-1H-benzimidazole | C8H4F3N3O2 | 详情 | 详情 | |
| (III) | 38448 | 2-(trifluoromethyl)-1H-benzimidazol-4-ylamine; 2-(trifluoromethyl)-1H-benzimidazol-4-amine | C8H6F3N3 | 详情 | 详情 | |
| (IV) | 25087 | 2,6-dichlorobenzoyl chloride | 4659-45-4 | C7H3Cl3O | 详情 | 详情 |
| (V) | 38449 | 2,6-dichloro-N-[2-(trifluoromethyl)-1H-benzimidazol-4-yl]benzamide | C15H8Cl2F3N3O | 详情 | 详情 | |
| (VI) | 38450 | tert-butyl 2-[4-[(2,6-dichlorobenzoyl)amino]-2-(trifluoromethyl)-1H-benzimidazol-1-yl]acetate | C21H18Cl2F3N3O3 | 详情 | 详情 | |
| (VII) | 38451 | 2-[4-[(2,6-dichlorobenzoyl)amino]-2-(trifluoromethyl)-1H-benzimidazol-1-yl]acetic acid | C17H10Cl2F3N3O3 | 详情 | 详情 | |
| (VIII) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |