4-Methylmorpholine → 6-(3-Fluorophenyl)-N-[1-(2,2,2-Trifluoroethyl)piperidin-4-Yl]pyridine-3-Carboxamide

Participants

Reaction Steps

1-(2,2,2-Trifluoroethyl)piperidin-4-amine was synthesized as in steps a-c of Example 1. To a 250 mL round bottom flask containing 6-(3-fluorophenyl)pyridine-3-carboxylic acid (see Example 3, Step A)(2.01 g, 9.25 mmol ) in DMA (35 mL) was added EDAC/EDC*HCl(1.95 g, 10.2 mmol), HOBt (1.38 g, 10.2 mmol), 1-(2,2,2-trifluoroethyl)piperidin-4-amine (1.85 g, 10.2 mmol) and NMM (2.23 mL, 20.4). After stirring at room temperature for 2 hours the reaction mixture was diluted with water (100 mL) and the resulting solid filtered and dried to give the desired product (2.96 g). LCMS (ES+) 4.55 min (TIC, 90%; 1H NMR purity >95%); 1H NMR (400 MHz, DMSO-d6) □ ppm 1.60 (dq, J=11.84, 3.48 Hz, 2 H) 1.81 (d, J=10.62 Hz, 2H) 2.44 (t, J=11.16 Hz, 2H) 2.50 (br. s., 2H) 2.94 (d, J=11.53 Hz, 2H) 3.74-3.87 (m, 1H) 7.32 (dt, J=8.37, 2.29 Hz, 1H) 7.57 (q, 1H) 7.96 (d, J=10.43 Hz, 1H) 8.01 (d, J=7.69 Hz, 1H) 8.14 (d, J=8.24 Hz, 1H) 8.28 (dd, J=8.24, 2.20 Hz, 1H) 8.49 (d, J=7.50 Hz, 1H) 9.07 (d, J=1.83 Hz, 1H); MS(ES+) 382 (M+1); HRMS (TOF, ES+) calculated for C19H19F4N3O+H+: 382.1542; observed 382.1548.

Provenance & Evidence