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

Participants

Reaction Conditions

Reaction Steps

2-Chloro-4-cyclobutylpyrimidine (50 mg, 0.297 mmol), 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 90 mg, 0.297 mmol), Pd2(dba)3 (27.2 mg, 0.030 mmol), XPhos (70.7 mg, 0.148 mmol), and potassium carbonate (82 mg, 0.593 mmol) were combined in t-amyl alcohol (0.99 ml). The mixture was purged with argon for 5 minutes, capped, and stirred at 90° C. overnight. The mixture was then cooled to room temperature and loaded directly on the column and was purified by silica gel chromatography (10% methanol/dichloromethane) to provide 98 mg (0.22 mol, 76% yield) of 4-(5-{3-[(4-cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a tan solid. MS APCI: [M+H]+ m/z 435.2. 1H NMR (600 MHz, d6-DMSO) δ 9.48 (s, 1H), 8.32 (d, J=4.8 Hz, 1H), 7.92 (s, 1H), 7.55 (dd, J=4.8 Hz, 5.4 Hz, 1H), 7.43 (s, 1H), 7.38 (s, 1H), 6.88 (s, 1H), 6.66 (d, J=5.4 Hz, 1H), 4.14 (s, 2H), 3.75 (m, 2H), 3.52 (m, 1H), 3.18 (m, 2H), 2.33-2.23 (m, 4H), 2.24 (s, 3H), 2.02 (m, 1H), 1.88 (m, 1H), 1.76 (m, 2H). rhSYK activity=+++

Provenance & Evidence