Ammonia → (R)-1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To (R)-methyl 1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxylate 61 (0.220 g, 0.46 mmol) was added ammonia (2 M in MeOH, 50 mL). The reaction mixture was heated to 75° C. in a sealed tube for 7 d, and concentrated in vacuo. Purification by flash column chromatography on silica gel (1% to 10% MeOH (2 M NH3) in DCM) gave (R)-1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxamide 62 (0.048 g, 23% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.26 (d, J=6.7 Hz, 3H), 1.76-1.84 (m, 4H), 2.24 (m, 1H), 2.52 (s, 3H), 2.67 (t, J=8.8 Hz, 2H), 2.95 (d, J=11.5 Hz, 2H), 3.43 (d, J=13.3 Hz, 1H), 3.48 (d, J=13.7 Hz, 1H), 3.71 (q, J=6.5 Hz, 1H), 6.71 (s, 1H), 7.19 (s, 1H), 7.05 (d, J=8.1 Hz, 1H), 7.20 (d, J=8.1 Hz, 1H), 7.22 (d, J=3.9 Hz, 1H), 7.31-7.38 (m, 6H), 8.22 (s, 1H), 9.73 (s, 1H). Mass spectrum: calculated for C26H31N5O3 461.2. found 462.3 (M++1).

Provenance & Evidence