反应详情

4-{4-[6-Amino-5-(5-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (34 mg) was dissolved in MeOH (20 mL), 1.0 M of HCl in Et2O (20 mL) was added, and the mixture was stirred at rt overnight. The solvent was removed in vacuo to give a brown oil. It was purified by Gilson HPLC eluting with H2O/CH3CN/0.1% formic acid mixtures to give the title compound contaminated with the corresponding formamide. This material was dissolved in MeOH (2 ml), aqueous NaOH (10 N, 2 ml) was added, and the solution was stirred at rt overnight. It was then treated with water (5 ml) and extracted with DCM (3×20 ml). The extracts were washed with water (2×20 ml), brine (20 ml), dried over MgSO4, filtered, and concentrated in vacuo, to give the title compound as a beige solid. 1H NMR (400 MHz, CD3OD): δ=1.79-1.92 (m, 2H), 1.98-2.06 (m, 2H), 2.63-2.70 (m, 2H), 2.90 (t, J=6.0 Hz, 2H), 3.06-3.14 (m, 2H), 3.18-3.24 (m, 2H), 4.06 (s, 2H), 4.15-4.23 (m, 1H), 6.82 (d, J=8.8 Hz, 1H), 6.85-6.88 (m, 1H), 7.05-7.12 (m, 1H), 7.44 (d, J=2.4 Hz, 1H), 7.66 (d, J=0.8 Hz, 1H), 7.83 (d, J=2.0 Hz, 1H), 7.91 (d, J=0.4 Hz, 1H). MS(ES+): m/z=394.14 (45) [MH+]. HPLC: tR=2.21 min (ZQ2, polar—5 min).

1. customThe solvent was removed in vacuo
2. customto give a brown oil
3. customIt was purified by Gilson HPLC
4. washeluting with H2O/CH3CN/0.1% formic acid