(4-Cyano-3-fluorophenyl)boronic acid → HCID 58504808, compound

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Reaction Steps

A mixture of 4-[(2R,5R)-2-(aminomethyl)-5-methyl-4-morpholinyl]-6-chloro-2-pyrimidinamine (0.809 g, 3.14 mmol) and (4-cyano-3-fluorophenyl)boronic acid (1.038 g, 6.29 mmol) in 1,4-dioxane (30 mL) and saturated aqueous NaHCO3 (10 mL) was degassed with nitrogen for 10 minutes. Pd(PPh3)4 (0.185 g, 0.16 mmol) was then added and the mixture was stirred at reflux under nitrogen for 16 hours. The mixture was then cooled and slowly quenched with 1 M HCl (75 mL), then washed with EtOAc (2×75 mL). The aqueous phase was then neutralized with saturated aqueous NaHCO3, brought to about pH 10 with saturated aqueous Na2CO3, and then extracted with 90/10 CH2Cl2/IPA (3×100 mL). The extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (40 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient). The product fractions were concentrated and azeotroped a few times with CH3CN to give the title compound (642 mg) as a yellow solid. LC-MS (ES) m/z=343 [M+H]+.

Provenance & Evidence