反应详情

{3-[1-(3-Benzyloxyphenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol: To a solution of 1-(3-benzyloxyphenyl)-8-chloro-3-(3-methylenecyclobutyl)-imidazo[1,5-a]pyrazine (345 mg, 0.86 mmol) in dry THF (5 mL) was added 9-BBN (2.6 mL, 1.3 mmol, 0.5 M in THF) dropwise at 0° C. under nitrogen atmosphere. The temperature was slowly warmed to rt overnight. Upon which time TLC showed the reaction was complete. The mixture was cooled to 0° C., and 2 mL 1N aq. NaOH and 0.4 mL 30% aq. H2O2 were added, the resulting mixture was stirred at 0° C. for 10 min, then rt for 30 min. The resulting white solid was filtered off, the filtrate was diluted with ethyl acetate (60 mL), washed with brine (3×20 mL), and dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, and the crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate), yielding the title compound as a yellow viscous oil, a mixture of cis and trans isomers. MS (ES, Pos.): MS (ES, Pos.): m/z 420/422 (3/1) [MH+]. 1H NMR (CDCl3, 400 MHz) δ 2.32 (br s, 1H), 2.60-2.85 (m, 5H), 3.88-4.11 (m, 3H), 5.36 (s, 2H), 7.27 (m, 1H), 7.48-7.69 (m, 9H), 7.77 (d, J=5.0 Hz, 1H).

1. temperatureThe mixture was cooled to 0° C.
2. waitrt for 30 min
3. filtrationThe resulting white solid was filtered off
4. additionthe filtrate was diluted with ethyl acetate (60 mL)
5. washwashed with brine (3×20 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate)