Cesium carbonate → HCID 66801371, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-(4-bromo-7-fluorothiazolo[5,4-c]pyridin-2-yl)-3-chlorobenzonitrile (150 mg, 0.41 mmol), (6-amino-2-methylpyrimidin-4-yl)-methanol (56 mg, 0.41 mmol), XantPhos (24 mg, 0.042 mmol) and Cs2CO3 (345 mg, 1.05 mmol) in 1,4-dioxane (2.5 mL) was added Pd2(dba)3 (20 mg, 0.022 mmol), and the reaction mixture was heated under argon at 80° C. for 24 hours. The resultant mixture was allowed to cool, diluted with water and extracted with ethyl acetate, then further extracted with 10% methanol in DCM (×5). The resultant insoluble material was filtered off, triturated twice with methanol and dried (50° C. under vacuum) to give the free base of the title compound as a solid (77 mg). The previously combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was purified by chromatography on silica (0-100% ethyl acetate in cyclohexane) to give a further crop of the free base of the title compound [(30 mg), total yield 107 mg, 61%]. The combined batches of free base were suspended in 2-propanol (2 mL), and a solution of hydrogen chloride in 1,4-dioxane (4 N, 2 mL) was added. The mixture was stirred for 1 hour, then the solvent was removed under reduced pressure, and the resultant residue was triturated with diethylether and dried (50° C. under vacuum) to give the title compound as an off-white solid (104 mg, 55%). 1H NMR (400 MHz, DMSO-d6): δ 11.76 (br s, 1H), 8.63 (s, 1H), 8.17-8.09 (m, 2H), 7.88 (t, J=8.1 Hz, 1H), 7.44 (br s, 1H), 4.58 (s, 2H), 2.57 (s, 3H). LCMS (Method C): RT=3.07, m/z: 427 [M+H+].

Provenance & Evidence