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

Temperature

90 °C

A flask was charged with a stir bar, 2,5-dichloro-4-methoxypyrimidine (69 mg, 0.38 mmol), Intermediate 15 (100 mg, 0.38 mmol), Pd2(dba)3 (35.2 mg, 0.038 mmol), XPhos (92 mg, 0.19 mmol), and potassium carbonate (106 mg, 0.77 mmol). The vial was fully evacuated and backfilled with argon three times. Fully degassed tert-amyl alcohol (1.30 mL) was added to the reaction mixture, which was sealed and stirred at 90° C. overnight. The reaction was then cooled to room temperature. The crude mixture was taken-up in DCM and directly purified by Chromatography on silica gel (0-100% ethyl acetate/hexanes) to provide 1-(5-{3-[(5-chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol (93 mg, 0.23 mmol, 60%) as a dark blue solid. MS ESI: [M+H]+ m/z 403.1. 1H NMR (500 MHz, dmso) δ 9.78 (s, 1H), 8.32 (s, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.46 (s, 1H), 7.10 (s, 1H), 6.50 (s, 1H), 4.05 (s, 3H), 2.56-2.50 (m, 2H), 2.36-2.27 (m, 5H), 1.94-1.82 (m, 2H). rhSYK activity=+++

1. additionA flask was charged with a stir bar
2. customThe vial was fully evacuated
3. additionFully degassed tert-amyl alcohol (1.30 mL) was added to the reaction mixture, which
4. customwas sealed
5. temperatureThe reaction was then cooled to room temperature
6. customdirectly purified by Chromatography on silica gel (0-100% ethyl acetate/hexanes)

ORD record

ord-9720554fbe2f426183814f32d53f4655

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08551984B2