【结 构 式】 |
【药物名称】Zinviroxime((Z)-isomer), Enviroxime, AR-336, LY-122772 【化学名称】(E)-2-Amino-6-benzoyl-1-(isopropylsulfonyl)benzimidazole oxime 【CA登记号】72301-79-2, 72301-78-1 ((Z)-isomer), 63198-97-0 (undefined stereoch.) 【 分 子 式 】C17H18N4O3S 【 分 子 量 】358.42201 |
【开发单位】Lilly (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antiviral Drugs |
合成路线1
The acetylation of 4-aminobenzophenone (I) with acetic anhydride in hot benzene gives 4-acetamidobenzophenone (II), which is nitrated with 90% HNO3 in acetic acid-acetic anhydride yielding 4-acetamido-3-nitrobenzophenone (III). The hydrolysis of (III) with H2SO4 affords 4-amino-3-nitrobenzophenone (IV), which is reduced with H2 over Raney-Ni in THF to give 3,4-diaminobenzophenone (V). The cyclization of (V) with cyanogen bromide in methanol-water gives rise to 2-amino-5-benzoylbenzimidazol (VI), which is treated with isopropylsulfonyl chloride (A) and NaH in dimethoxyethane affording 2-amino-1-isopropylsulfonyl-6-benzoylbenzimidazol (VII). Finally, this compound is treated with hydroxylamine hydrochloride in refluxing methanol.
【1】 Paget, C.J.; et al.; DE 2638551 . |
【2】 Castaner, J.; Hopkins, S.J.; AR-336. Drugs Fut 1980, 5, 3, 120. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 18477 | 2-propanesulfonyl chloride | 10147-37-2 | C3H7ClO2S | 详情 | 详情 |
(I) | 39112 | 3-Aminobenzophenone; (3-aminophenyl)(phenyl)methanone | 2835-78-1 | C13H11NO | 详情 | 详情 |
(II) | 39113 | N-(3-benzoylphenyl)acetamide | 58202-86-1 | C15H13NO2 | 详情 | 详情 |
(III) | 39114 | N-(5-benzoyl-2-nitrophenyl)acetamide | C15H12N2O4 | 详情 | 详情 | |
(IV) | 39115 | (3-amino-4-nitrophenyl)(phenyl)methanone | C13H10N2O3 | 详情 | 详情 | |
(V) | 12830 | (3,4-Diaminophenyl)phenylmethanone; 3,4-Diaminobenzophenone | 39070-63-8 | C13H12N2O | 详情 | 详情 |
(VI) | 39116 | (2-amino-1H-benzimidazol-6-yl)(phenyl)methanone | C14H11N3O | 详情 | 详情 | |
(VII) | 39117 | [2-amino-1-(isopropylsulfonyl)-1H-benzimidazol-6-yl](phenyl)methanone | C17H17N3O3S | 详情 | 详情 |