反应详情

温度

-78 °C

A solution of 2N ammonia in isopropyl alcohol (350 mL) and THF (30 mL, 0.4 mol) was added to 8-chloro-1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazine (19.91 g, 0.04612 mol) in a Parr bomb and cooled to −78° C. Ammonia was bubbled into the solution for 8-10 min. The bomb was sealed, stirred and heated to at 110° C. over 3 d. The solvent was then evaporated in vacuo and purified by flash silica gel chromatography (wetted with CHCl3, dried loaded with silica, and eluted with 8% (7N NH3) MeOH in CHCl3), which afforded the title compound; 1H NMR (CDCl3, 400 MHz) δ 7.31 (1H, d, J=5.01), 7.16 (1H, d, J=6.25), 5.83 (2H, s), 3.49 (1H, m), 3.06 (1H, m), 2.76 (4H, m), 2.64 (8H, m), 2.46 (3H, s); MS (ES+): m/z 412.89/413.91 (50/10) [MH+]; HPLC: tR=0.31 min. (OpenLynx, polar—5 min.).

1. customAmmonia was bubbled into the solution for 8-10 min
2. customThe bomb was sealed
3. temperatureheated to at 110° C. over 3 d
4. customThe solvent was then evaporated in vacuo
5. custompurified by flash silica gel chromatography (wetted with CHCl3, dried loaded with silica, and eluted with 8% (7N NH3) MeOH in CHCl3), which