Potassium Carbonate → 4-(5-{3-[(5-Chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one

Participants

Reaction Conditions

Reaction Steps

A sealed tube was charged with a stir bar, 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 75 mg, 0.248 mmol), 2,5-dichloro-4-methoxypyrimidine (44 mg, 0.248 mmol), potassium carbonate (69 mg, 0.496 mmol), Pd2(dba)3 (23 mg, 0.025 mmol), and XPhos (59 mg, 0.124 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed t-amyl alcohol (0.83 ml) was added and the tube was sealed and heated at 90° C. for overnight. The resulting slurry was diluted with methanol, absorbed onto 1.5 g of silica, and purified via silica gel chromatography (0-20% methanol in ethyl acetate) to afford 44 mg (1.0 mmol, 40% yield) of 4-(5-{3-[(5-chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a light yellow solid. MS APCI: [M+H]m/z 445.1. 1H NMR (500 MHz, dmso) δ 9.72 (s, 1H), 8.30 (s, 1H), 7.77 (s, 1H), 7.59 (t, J=5.0 Hz, 1H), 7.48 (s, 1H), 7.30 (s, 1H), 6.95 (s, 1H), 4.15 (s, 2H), 4.05 (s, 3H), 3.78 (m, 2H), 3.21 (m, 2H), 2.26 (s, 3H), 1.77 (m, 2H). rhSyk=+++

Provenance & Evidence