Hydrochloric Acid → 3-Chloro-5-fluoro-2-{7-fluoro-4-[6-(2-hydroxyethylamino)-2-methylpyrimidin-4-ylamino]pyrazolo[4,3-c]pyridin-2-yl}benzonitrile hydrochloride salt

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Reaction Conditions

Reaction Steps

A mixture of 2-(4-chloro-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-5-fluorobenzonitrile (185 mg, 0.5 mmol), 2-(6-amino-2-methylpyrimidin-4-ylamino)ethanol (101 mg, 0.6 mmol), Pd2(dba)3 (11 mg, 0.0125 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. The reaction mixture was heated at 80° C. in a sealed vial overnight. After cooling, the resultant mixture was diluted with ethyl acetate and washed with water. 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 (0-2% methanol in ethyl acetate) to afford crude product. This was dissolved in 1.25 N HCl in propan-2-ol solution (10 mL) and was stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure, and diethyl ether was added and the mixture was stirred for 5 minutes. The precipitate was filtered off and dried to afford the title compound as an off-white solid (68 mg, 28% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.35-8.29 (m, 2H), 8.07 (s, 1H), 7.13 (br s, 1H), 3.66-3.59 (m, 2H), 3.59-3.49 (m, 2H), 2.59 (s, 3H). LCMS (Method B): RT=3.13 min, m/z: 457 [M+H+].

Provenance & Evidence