Cesium carbonate → 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-((6-chloropyrimidin-4-yl)oxy)pyridin-2-amine (0.50 g, 2.246 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.467 g, 2.246 mmol), and Cs2CO3 (1.463 g, 4.49 mmol) in dioxane/H2O (5:1, 6 mL) was sparged with argon, treated with Pd(PPh3)4 (0.260 g, 0.225 mmol), sparged again with argon and heated at 90° C. overnight. The mixture was cooled to RT, the solids removed via filtration, rinsed with dioxane and the filtrate concentrated to dryness. The material was treated with EtOAc, the solid collected via filtration, rinsed with EtOAc and H2O and dried to obtain product. The layers of the filtrate were separated, the organic layer washed with brine, dried over Na2SO4, concentrated to dryness, triturated with EtOAc and the solid collected via filtration and combined with the above-isolated product to afford 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine (410 mg, 68%). 1H NMR (400 MHz, DMSO-d6): δ 8.60 (d, J=1.1 Hz, 1H), 8.44 (s, 1H), 8.12 (s, 1H), 7.78 (d, J=2.9 Hz, 1H), 7.30-7.25 (m, 2H), 6.48 (d, J=8.9 Hz, 1H), 5.94 (s, 2H), 3.88 (s, 3H); MS (ESI) m/z: 269.1 (M+H+).

Provenance & Evidence