Potassium Carbonate → Tert-butyl (3-(4-fluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

Combine 1-(5-(7-chloro-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-fluoro-3-methylbutyl)urea (8.1 g, 18.71 mmol), t-butylcarbamate (6.58 g, 56.1 mmol), potassium carbonate (7.76 g, 56.1 mmol), palladium (II) acetate (0.420 g, 1.871 mmol), and Xantphos (1.083 g, 1.871 mmol) in dioxane (100 mL). Sparge the mixture with argon and sonication for 10 min, then heat at 95° C. overnight. Dilute with EtOAc (100 mL), filter through diatomaceous earth, and wash the filter cake with EtOAc. Evaporate the filtrate and purify by silica gel chromatography (hexane/EtOAc) to yield the title compound (5.81 g, 60.5%). Dissolve the title compound (5.81 g, 11.31 mmol) in THF (100 mL), treat with Si-Thiol (Pd Scavenger) (1.3 mM/g, 9.4 mmol) and stir overnight at RT. Remove the solids via filtration, concentrate the filtrate and dry under high vacuum to afford the title compound (5.81 g, 100%). 1H NMR (400 MHz, DMSO-d6): δ 10.02 (s, 1H); 9.06 (d, J=0.8 Hz, 1H); 8.37 (s, 1H); 8.13 (d, J=24.9 Hz, 2H); 7.96 (d, J=8.5 Hz, 1H); 7.20 (d, J=12.3 Hz, 1H); 6.57 (t, J=5.7 Hz, 1H); 3.11-3.18 (m, 2H); 2.36 (s, 3H); 1.95 (s, 3H); 1.74 (dt, J=19.9, 7.5 Hz, 2H); 1.50 (s, 9H); 1.29 (d, J=22 Hz, 6H; MS (ESI) m/z: 514.3 (M+H+).

Provenance & Evidence