Dimethylformamide → 5-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-N-(3-(dimethylamino)propyl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-[3-(dimethylamino)propyl]-5-iodo-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (10 g, 19.71 mmol), 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)benzonitrile (8.9 g, 29.55 mmol), water (0.71 g), N,N-dimethylformamide (100 mL) and diispropylethylamine (7.64 g, 59.14 mmol) was purged with nitrogen for 10 minutes. To the above mixture was charged 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (“Pd-118” ex. Johnson Matthey, 642.38 mg, 985.62 moles) and the mixture heated to 40° C. for 12 h. The reaction mixture was cooled to room temperature and was added to a mixture of isopropanol (100 mL) and water (200 mL). The resulting mixture was stirred for 18 h. The precipitate was filtered, washed with water (50 mL) and dried under vacuum at 50° C. for 12 h to afford the title product as a brown solid (6.2 g, 56%); 1H NMR (400 MHz, DMSO-d6) δ 9.33 (t, J=5.77 Hz, 1 H), 8.07 (s, 1 H), 7.92-7.98 (m, 3 H), 7.91 (s, 1 H), 7.82-7.89 (m, 2 H), 7.72 (d, J=8.03 Hz, 1 H), 7.67 (d, J=8.53 Hz, 2 H), 6.73 (d, J=1.51 Hz, 1 H), 3.26 (q, J=6.86 Hz, 2 H), 2.25 (t, J=6.78 Hz, 2 H), 2.13 (s, 6 H), 1.75 (s, 3 H), 1.59 (p, J=7.03 Hz, 2 H); LCMSm/z: 549 [M+]

Provenance & Evidence