Ammonia → 1-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine
反応式
[Br:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][N:15]3[C:18]([C:21]([F:24])([F:23])[F:22])=[N:19][N:20]=[C:14]3[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7](Cl)[C:6]=12.[NH3:25].CC(O)C>>[Br:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][N:15]3[C:18]([C:21]([F:24])([F:23])[F:22])=[N:19][N:20]=[C:14]3[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:25])[C:6]=12参加物
反応条件
- 温度
- 120 °C
実験手順
To a 75 ml sealed vessel was charged with 7-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (595 mg, 1.408 mmol) along with ammonia in IPA (2N, 0.704 ml, 1.408 mmol). The vessel was sealed with screw cap and heated in an oil bath of 120° C. for 18 hrs overnight. LC-MS showed complete conversion of starting material to product. The mixture was then cooled to room temperature, solid (gel) precipitated and was filtered, washed with IPA and dried to afford 1-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine (250 mg). The filtrate was concentrated and the residue was purified by MPLC (12 g silica gel, 0 to 10% methanol in methylenechloride, 28 CV) to afford another batch of product. Totally 1-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine (386 mg, 0.957 mmol, 68.0% yield) was obtained. LC-MS: C12H10BrF3N8,402. found 403.08 [M+H]+, RT=1.09 min.
後処理
- customTo a 75 ml sealed vessel
- customThe vessel was sealed with screw
- customcap
- temperatureThe mixture was then cooled to room temperature
- customsolid (gel) precipitated
- filtrationwas filtered
- washwashed with IPA
- customdried
出典と根拠
- ORDレコード
- ord-b2b8d769395b47c5873850d3543a416d
- 出典データセット
- uspto-grants-2016_09
- 特許番号
- US09446130B2
反応ノート
読み込み中…