Dichloromethane → 3-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-hydroxyethyl)quinoline-2-carboxamide

Participants

Reaction Steps

A mixture of benzyl [2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-(1-hydroxyethyl)quinolin-3-yl]carbamate (0.020 g, 0.031 mmol) and 10% Pd on carbon (0.100 g, 0.0940 mmol) in MeOH (20 mL) was hydrogenated under 20 psi of H2 for 2 h. The catalyst was removed by vacuum filtration, and the clear filtrate was concentrated under reduced pressure. To the residue, a mixture of DCM (1.0 mL) and TFA (1.0 mL, 13 mmol) was added. The resulting mixture was stirred at room temperature for 1 h. The mixture was then concentrated under reduced pressure and the residue was diluted with MeOH and neutralized with small amount of NH4OH. The mixture was filtered and purified by prep LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH) to give the title compound as white powder. LCMS calc. for C22H27N6O2 (M+H)+: m/z=407.3. Found: 407.2. 1H NMR (500 MHz, DMSO) δ 9.40 (s, 1H), 8.26 (d, J=5.3 Hz, 1H), 7.79 (s, 1H), 7.67 (d, J=8.6 Hz, 1H), 7.54 (s, 1H), 7.51 (dd, J=8.7, 1.5 Hz, 1H), 7.16 (d, J=5.3 Hz, 1H), 6.84 (s, 2H), 5.29 (d, J=3.8 Hz, 1H), 4.89-4.79 (m, 1H), 3.20 (d, J=10.9 Hz, 1H), 3.16 (d, J=4.2 Hz, 1H), 3.15-3.06 (m, 1H), 2.71-2.63 (m, 1H), 2.47-2.41 (m, 1H), 1.95 (d, J=12.9 Hz, 1H), 1.92-1.82 (m, 2H), 1.41 (d, 3H), 1.27-1.16 (m, 1H) ppm.

Provenance & Evidence