Cesium carbonate → {6-[2-(2-Chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-2-methylpyrimidin-4-yl}-methanol hydrochloride salt

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Reaction Conditions

Reaction Steps

A mixture of 4-bromo-2-(2-chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (172 mg, 0.5 mmol), 4-amino-2,6-dimethylpyrimidine (83 mg, 0.6 mmol), Pd2(dba)3 (11 mg, 0.013 mmol), Xantphos (29 mg, 0.05 mmol) and cesium carbonate (326 mg, 1.0 mmol) in dioxane (5 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 80° C. in a sealed vial overnight. The resultant mixture was allowed to cool to room temperature, before being partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (80-100% ethyl acetate in cyclohexane). The resultant residue was stirred with HCl (1.25 N in propan-2-ol, 5.0 mL) for 1 hour. The resultant mixture was concentrated under reduced pressure and the solid obtained was triturated with diethyl ether, filtered and dried to afford the title compound as a white solid (153 mg, 70% yield). 1H NMR (400 MHz, DMSO-d6): δ 12.25 (br s, 1H), 9.48 (s, 1H), 8.25 (br s, 1H), 8.15 (d, J=3.6 Hz, 1H), 7.83-7.76 (m, 1H), 7.74-7.66 (m, 2H), 4.70 (s, 2H), 2.67 (s, 3H). LCMS (Method B): RT=2.96 min, m/z: 403 [M+H+].

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