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

Participants

Reaction Conditions

Reaction Steps

2-Chloro-4-ethenylpyrimidine (250 mg, 1.78 mmol), 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 538 mg, 1.78 mmol), potassium carbonate (490 mg, 3.56 mmol), Pd2(dba)3 (163 mg, 0.18 mmol), and XPhos (420 mg, 0.89 mmol) were added to an oven-dried vessel which was purged and flushed with argon. t-Amyl alcohol (5 ml) was added and the reaction mixture was heated at 90° C. for 18 h. The mixture was then cooled to room temperature, diluted with water and brine and extracted with ethyl acetate (3×). The organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The residual orange oil was purified via silica gel column chromatography (0-10% methanol/dichloromethane) to provide 188 mg of 4-(5-{3-[(4-ethenylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a yellow-orange solid. MS APCI: [M+H]+ m/z 407.1. 1H NMR (500 MHz, CDCl3) δ 8.37 (d, 1H, J=4.9 Hz), 7.77 (s, 1H), 7.50 (s, 1H), 7.42 (s, 1H), 7.24 (s, 1H), 6.89 (s, 1H), 6.68 (d, 1H, J=5.2 Hz), 6.67-6.46 (m, 2H), 5.65 (m, 1H, J=9.1 Hz), 4.26 (m, 2H), 3.85 (m, 2H), 3.32 (m, 2H), 2.33 (s, 3H), 1.99 (m, 2H). rhSyk=+++.

Provenance & Evidence