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

Participants

Reaction Conditions

Reaction Steps

In an oven-dried vial was added 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 77 mg, 0.26 mmol), 2-chloro-4-cyclopropylpyrimidine (44 mg, 0.26 mmol), potassium carbonate (70 mg, 0.51 mmol), XPhos (61 mg, 0.13 mmol), and Pd2(dba)3 (23 mg, 0.025 mmol). The tube was evacuated and backfilled with argon 3×. Degassed t-amyl alcohol (0.85 ml) was added, and the tube was sealed and heated to 90° C. for 15 h. The mixture was then cooled to room temperature and purified by Combiflash (0-70% ethyl acetate/hexanes followed by 0-20% methanol/dichloromethane) to provide 77 mg (0.18 mmol, 72%) of 4-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a yellow foam. MS APCI: [M+H]+ m/z 421.2. 1H NMR (500 MHz, CDCl3) δ 8.16 (d, J=5.6 Hz, 1H), 7.75 (s, 1H), 7.44 (s, 2H), 7.13 (s, 1H), 6.91 (s, 1H), 6.65 (d, J=5.5 Hz, 1H), 6.00 (s, 1H), 4.27 (d, J=13.9 Hz, 2H), 3.98-3.79 (m, 2H), 3.38 (dd, J=5.6 Hz, 11.2 Hz, 2H), 2.33 (s, 3H), 2.04 (d, J=4.0 Hz, 3H), 1.26 (t, J=7.3 Hz, 2H), 1.11 (dd, J=3.2 Hz, 8.3 Hz, 2H). rhSyk=+++.

Provenance & Evidence