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【结 构 式】 
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【药物名称】Ketazolam, Anseren, Unakalm, Loftran, Anxon 【化学名称】11-Chloro-2,8-dimethyl-12b-phenyl-8,12b-dihydro-4H-[1,3]oxazino[3,2-b][1,4]benzodiazepine-4,7(6H)-dione 【CA登记号】27223-35-4 【 分 子 式 】C20H17ClN2O3 【 分 子 量 】368.82309 |
【开发单位】Pfizer (Originator), FAES (Not Determined), Novartis (Not Determined) 【药理作用】Anxiolytics, Generalized Anxiety Disorder (GAD), Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Benzodiazepines |
合成路线1
The methylation of 2-amino-5-chlorobenzophenone (I) with dimethyl-sulfate affords the 5-chloro-2-methylaminobenzophenone (II), which is conden-sed with bromoacetyl bromide (A) to yieId 2-(2-bromo-N-methylacetamido)-5-chlorobenzophenone (III). The amonolysis of (III) with ammonia in methanol gives 2-(2-amino-N-methylacetamido)-5-chlorobenzophenone (IV), which is finally condensed with diketene (B) in refluxing acetone. This product can also be obtained by condensation of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (V) with acetyl chloride (C) and triethylamine in ether or with diketene (B) in acetone.
| 【1】 Szmuszkovicz, J.; et al.; Tetrahedron Lett 1971, 39, 39, 3665. |
| 【2】 Szmuszkovicz, J.; Oxazinobenzodiazepine derivatives. DE 1947226; ES 371392; FR 2018432; GB 1222294 . |
| 【3】 Szmuszkovicz, J.; Process for the preparation of 11-chloro-8,12b-dihydro-2,8-dimethyl-12b-phenyl-4H-[1,3]oxazino[3,2-d]benzodiazepine-4,7-6H-dione. CH 530414; JP 49025953B; NL 7014824; US 3575965 . |
| 【4】 Castaner, J.; Chatterjee, S.S.; Ketazolam. Drugs Fut 1976, 1, 6, 293. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 详情 | 详情 |
| (A) | 14005 | 2-Bromoacetyl bromide; Bromoacetyl bromide | 598-21-0 | C2H2Br2O | 详情 | 详情 |
| (I) | 10279 | (2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone | 719-59-5 | C13H10ClNO | 详情 | 详情 |
| (II) | 33972 | [5-chloro-2-(methylamino)phenyl](phenyl)methanone | 1022-13-5 | C14H12ClNO | 详情 | 详情 |
| (III) | 33973 | N-(2-benzoyl-4-chlorophenyl)-2-bromo-N-methylacetamide | C16H13BrClNO2 | 详情 | 详情 | |
| (IV) | 33974 | 2-amino-N-(2-benzoyl-4-chlorophenyl)-N-methylacetamide | C16H15ClN2O2 | 详情 | 详情 | |
| (V) | 33975 | 7-chloro-1-methyl-5-phenyl-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one | C16H15ClN2O | 详情 | 详情 | |
| (C) | 19273 | acetyl chloride | 75-36-5 | C2H3ClO | 详情 | 详情 |