【结 构 式】 |
【分子编号】34097 【品名】[5-chloro-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl]phenyl](phenyl)methanone 【CA登记号】 |
【 分 子 式 】C17H14ClN3O2 【 分 子 量 】327.76988 【元素组成】C 62.3% H 4.31% Cl 10.82% N 12.82% O 9.76% |
合成路线1
该中间体在本合成路线中的序号:(VI)The reaction of 2,6-dichloro-4-phenylquinoline (I) with refluxing hydrazine hydrate gives 6-chloro-2-hydrazino-4-phenylquinoline (II), which is cyclocondensed with triethyl orthoacetate (A) in refluxing xylene yielding 7-chloro-1-methyl-5-phenyl-s-triazolo[4,3-a]quinoline (III). The oxidation of (III) to 5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone (V) can be performed with sodium periodate and ruthenium dioxide in acetone-water, or first with ozone in CH2Cl2 giving 4-(2-benzoyl-4-chlorophenyl)-5-methyl-4H-1,2,4-triazol-3-carboxaldehyde (IV), which is then oxidized to (V) with silver oxide in methanol. The condensation of (V) with formaldehyde in xylene at 125 C affords 5-chloro-2-(3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl)benzophenon (VI), which by reaction with PBr3 in chloroform is converted into 5-chloro-2-(3-bromoethyl-5-methyl-4H-1,2,4-triazol-4-yl)benzophenon (VII). Finally, this product is cyclized with ammonia in THF - methanol.
【1】 Hester, J.B. Jr.; Process for the production of triazolobenzodiazepines and intermediates. DE 2203782; FR 2124559; GB 1374822; GB 1374823; GB 1374824; GB 1374825; JP 49066679; US 3709898 . |
【2】 Castaner, J.; Chatterjee, S.S.; Alprazolam. Drugs Fut 1976, 1, 12, 551. |
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) | 12940 | 1,1-Diethoxyethyl ethyl ether; 1,1,1-Triethoxyethane; Triethyl orthoacetate | 78-39-7 | C8H18O3 | 详情 | 详情 |
(I) | 34092 | 2,6-dichloro-4-phenylquinoline | C15H9Cl2N | 详情 | 详情 | |
(II) | 34093 | 6-chloro-2-hydrazino-4-phenylquinoline | C15H12ClN3 | 详情 | 详情 | |
(III) | 34094 | 7-chloro-1-methyl-5-phenyl[1,2,4]triazolo[4,3-a]quinoline | C17H12ClN3 | 详情 | 详情 | |
(IV) | 34095 | 4-(2-benzoyl-4-chlorophenyl)-5-methyl-4H-1,2,4-triazole-3-carbaldehyde | C17H12ClN3O2 | 详情 | 详情 | |
(V) | 34096 | [5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)phenyl](phenyl)methanone | C16H12ClN3O | 详情 | 详情 | |
(VI) | 34097 | [5-chloro-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl]phenyl](phenyl)methanone | C17H14ClN3O2 | 详情 | 详情 | |
(VII) | 34098 | [2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol-4-yl]-5-chlorophenyl](phenyl)methanone | C17H13BrClN3O | 详情 | 详情 |