反应详情

To a solution of 4-{4-[6-amino-5-(4-methylisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (79.1 mg, 0.163 mmol) in 1,4-dioxane (2.0 mL, 26 mmol) was added 4.0 M of HCl in 1,4-dioxane (2.0 mL), and the mixture was stirred at ambient temperature for 3 h. Almost immediately an off-white solid precipitated. The solid was filtered off, washed with MTBE, and dried in vacuo overnight to give the title compound as an off-white solid. It appeared to be slightly hygroscopic during the filtration; however, after the washing and initial drying it appeared to be non-hygroscopic. 1H NMR (400 MHz, DMSO-d6): δ=14.6 (very brs, 1H), 9.68 (s, 1H), 9.37-9.24 (brm, 1H), 9.24-9.10 (brm, 1H), 8.55 (d, J=2.0 Hz, 1H), 8.47 (d, J=7.6 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.39 (s, 1H), 8.38 (d, J=7.6 Hz, 1H), 8.14 (t, J=7.2 Hz, 1H), 8.05 (s, 1H), 7.98 (t, J=7.6 Hz, 1H), 7.81 (brs, 2H), 4.54-4.45 (mc, 1H), 3.35 (brd, J=12.6 Hz, 2H), 3.07 (brq, J=11.2 Hz, 2H), 2.59 (s, 3H), 2.26-2.09 (m, 4H). MS(ES+): m/z=385.17 (96) [MH+], 302.1 (100) [MH+-piperidine]. HPLC: tR=0.65 & 1.72 min (peak splitting; polar—5 min, ZQ3).

1. customAlmost immediately an off-white solid precipitated
2. filtrationThe solid was filtered off
3. washwashed with MTBE
4. customdried in vacuo overnight