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【结 构 式】 
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【药物名称】 【化学名称】4-[2-[2-[3-(Biphenyl-4-yl)-5-methyl-4H-1,2,4-triazol-4-yl]phenoxy]ethyl]morpholine 【CA登记号】258878-68-1 【 分 子 式 】C27H28N4O2 【 分 子 量 】440.54981 |
【开发单位】Yamanouchi (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Vasopressin V1a Antagonists |
合成路线1
The reaction of 2-(benzyloxy)aniline (I) with acetic anhydride and pyridine gives the acetanilide (II), which is treated with P2S5 in hot toluene to yield the thioacetamide (III). The reaction of (III) with methyl iodide and K2CO3 in hot acetonitrile affords the methylated thioimidate (IV), which is cyclized with biphenyl-4-carbohydrazide (V) in hot DMF to provide 4-(2-benzyloxyphenyl)-3-(4-biphenylyl)-5-methyl-4H-1,2,4-triazole (VI). The hydrogenation of (VI) with H2 over Pd/C in methanol gives the corresponding phenol (VII), which is finally alkylated by means of 4-(2-chloroethyl)morpholine (VIII) and NaH in hot DMF to yield the target triazole. (1,2)
| 【1】 Kakefuda, A.; Suzuki, T.; Tobe, T.; Tahara, A.; Sakamoto, S.; Tsukamoto, S.-I.; Discovery of 4,5-diphenyl-1,2,4-triazole derivatives as a novel class of selective antagonists for the human V1A receptor. Bioorg Med Chem 2002, 10, 6, 1905. |
| 【2】 Suzuki, T.; Murakami, T.; Tobe, T.; Tahara, A. (Yamanouchi Pharmaceutical Co., Ltd.); Novel triazole derivs.. WO 0158880 . |
| 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) | 18065 | 2-(benzyloxy)aniline; 2-(benzyloxy)phenylamine | C13H13NO | 详情 | 详情 | |
| (II) | 56977 | N-[2-(benzyloxy)phenyl]acetamide | C15H15NO2 | 详情 | 详情 | |
| (III) | 56978 | N-[2-(benzyloxy)phenyl]ethanethioamide | C15H15NOS | 详情 | 详情 | |
| (IV) | 56979 | methyl N-[2-(benzyloxy)phenyl]ethanimidothioate | C16H17NOS | 详情 | 详情 | |
| (V) | 56980 | 4-Biphenylcarboxylic acid hydrazide; 4-Phenylbenzhydrazide | 18622-23-6 | C13H12N2O | 详情 | 详情 |
| (VI) | 56981 | benzyl 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl ether; 4-[2-(benzyloxy)phenyl]-3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazole | C28H23N3O | 详情 | 详情 | |
| (VII) | 56982 | 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenol | C21H17N3O | 详情 | 详情 | |
| (VIII) | 27355 | 4-(2-chloroethyl)morpholine | 3647-69-6 | C6H12ClNO | 详情 | 详情 |