反应详情

(3S,4S)-tert-butyl 4-((3-amino-6-bromo-7-fluoroquinolin-4-yl)amino)-3-fluoropiperidine-1-carboxylate (27 g, 0.059 mol) was heated in triethylorthoacetate (150 mL) under N2 atmosphere for 5 h at 120° C. The reaction was monitored by TLC (5% MeOH/DCM). The volatiles were concentrated under vacuum, the obtained crude product was purified by column chromatography on silica gel (0-3% MeOH/DCM) to afford (3S,4S)-tert-butyl 4-(8-bromo-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-3-fluoropiperidine-1-carboxylate (15 g, yield from two steps). 1HNMR (CDCl3, 400 MHz): δ 9.28-9.23 (d, 1H), 8.43-8.34 (dd, 1H), 8.01-7.99 (d, 1H), 5.60-5.35 (m, 1H), 5.25-4.85 (m, 1H), 4.75-4.35 (m, 2H), 3.15-2.95 (m, 2H), 2.79 (s, 3H), 2.40-2.05 (m, 2H), 1.57 (s, 9H); LCMS: 100%, m/z=480.8 (M+); HPLC: 97.31%.

1. concentrationThe volatiles were concentrated under vacuum
2. customthe obtained crude product
3. customwas purified by column chromatography on silica gel (0-3% MeOH/DCM)