Cesium carbonate → 8-[[2-[(1,3-Dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-2-methyl-3,4-dihydroisoquinolin-1-one

Participants

Reaction Conditions

Reaction Steps

A suspension of 8-amino-2-methyl-3,4-dihydroisoquinolin-1-one (23.06 mg, 0.13 mmol), N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (50 mg, 0.13 mmol, Ex. 2.02), palladium(II) acetate (1.469 mg, 6.54 μmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (7.57 mg, 0.01 mmol) and cesium carbonate (85 mg, 0.26 mmol) in dioxane (1 ml) was stirred at 80° C. overnight under nitrogen. The same reactants were dissolved in DMA (1 mL) and sealed into a microwave tube. Argon was bubbled through the reaction mixture then the reaction was heated to 150° C. over a period of 30 minutes in a microwave reactor. The crudes were combined, poured onto a silica gel column and purified by flash chromatography eluting with 0 to 5% MeOH in EtOAc/DCM (1:1). The solvent was evaporated to dryness. Trituration with a few drops of MeCN gave a solid which was taken up into Et2O, collected by filtration and dried to afford the title compound (19 mg, 33.7%) as a white solid. 1H NMR spectrum (500 MHz, CDCl3): 2.16 (s, 3H), 2.90-2.99 (m, 2H), 3.14 (s, 3H), 3.51-3.58 (m, 2H), 3.79 (s, 3H), 5.94 (s, 1H), 6.42 (s, 1H), 6.90 (d, 1H), 7.20 (dd, 1H), 7.29 (d, 1H), 7.37 (s, 1H), 8.26 (s, 1H), 11.13 (s, 1H); Mass spectrum: ESI+ MH+ 431.

Provenance & Evidence