Cesium carbonate → HCID 66801376, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(4-bromothiazolo[5,4-c]pyridin-2-yl)-3-chloro-5-fluorobenzonitrile (98 mg, 0.26 mmol), (6-aminopyrimidin-4-yl)-methanol (33 mg, 0.26 mmol), Pd2(dba)3 (12 mg, 0.013 mmol), XantPhos (15 mg, 0.026 mmol) and cesium carbonate (219 mg, 0.67 mmol) in 1,4-dioxane (2 mL) was heated under argon at 80° C. for 16 hours. The cooled reaction mixture was diluted with water and extracted five times with ethyl acetate, then three times with 10% methanol in DCM. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by chromatography on silica (20-100% ethyl acetate in cyclohexane) to yield the free base of the title compound (41 mg, 38%). This material was suspended in DCM (2 mL) and 2-propanol (0.5 mL), and a solution of hydrogen chloride in 2-propanol (1.25 N, 1 mL) was added and the resultant mixture was stirred for 10 minutes. The solvent was removed under reduced pressure and the resultant residue was triturated three times with diethylether and dried (50° C. under vacuum) to give the title compound as an off-white solid (44 mg). 1H NMR (400 MHz, DMSO-d6): δ 8.93 (s, 1H), 8.59 (d, J=5.6 Hz, 1H), 8.28-8.23 (m, 2H), 8.05 (d, J=5.6 Hz, 1H), 7.87 (br s, 1H), 4.64 (s, 2H). LCMS (Method C): RT=3.14, m/z: 413 [M+H+].

Provenance & Evidence