Sodium Carbonate → 1-[5-(2-Fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol

Participants

Reaction Conditions

Reaction Steps

To a solution of the product of Step 2 (383 mg, 1.0 mmol) in DMF (2 mL) and aqueous sodium carbonate (2 M, 1.5 mL, 3.0 mmol) in a microwave vial was added Intermediate 1 (234 mg, 1.0 mmol), and PdCl2(dppf)-dichloromethane adduct (82 mg, 0.1 mmol) under dry nitrogen. The vial was sealed and the reaction was heated in a microwave at 85° C. for 2 hours. The reaction was cooled to room temperature, diluted with ethyl acetate, washed with water, then brine and was dried over sodium sulfate. The organic was concentrated after filtration and was purified by flash chromatography (25:75 ethyl acetate:hexanes) to afford 1-[5-(2-fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol as an off-white foamy solid (102 mg, 0.249 mmol, 24.9%). 1H NMR (500 MHz, CDCl3): δ 8.66 (d, J=4.9 Hz, 1H); 8.07 (s, 1H); 8.03 (d, J=6.1 Hz, 1H); 7.82 (s, 1H); 7.50 (dt, J=8.8, 3.4 Hz, 1H); 7.16 (t, J=9.6 Hz, 1H); 7.07 (d, J=4.9 Hz, 1H); 4.07 (s, 1H); 2.77-2.70 (m, 2H); 2.59-2.49 (m, 2H); 2.13-1.98 (m, 2H). rhSYK activity=++

Provenance & Evidence