Ethanol → N-[4-(4-Cyano-3,5-difluorophenyl)-2-pyrimidinyl]acetamide

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-(2-amino-4-pyrimidinyl)-2,6-difluorobenzaldehyde (5.69 g, 24.2 mmol) in EtOH (50 mL) and water (150 mL), were added sodium carbonate (2.82, 26.6 mmol) and hydroxylamine hydrochloride (1.85 g, 26.6 mmol), and the resulting mixture was stirred at 100° C. until the starting material was consumed as judged by LCMS (˜2 hours). The reaction mixture was concentrated, and the resulting tan solid was washed with water and filtered. The aqueous washings were extracted with EtOAc, and the combined organic layers were concentrated. The concentrated organic extract and the filter cake were combined and suspended in acetic anhydride (used as solvent, ˜150 mL), and the reaction mixture was stirred at 100° C. until the oxime intermediate was completely converted to the nitrile (˜5 days). The reaction mixture was concentrated and co-evaporated with EtOH, and the resulting solid was triturated with CH3OH to afford the title compound (2.4 g, 36%) as a sandy tan solid. The filtrate was treated with saturated aqueous NaHCO3 and K2CO3, and the basic solution was stirred overnight at room temperature converting the bis-acetyl by-product to the title compound. The basic solution was filtered, and the filtrate was concentrated. The resulting solid was triturated with CH3OH and washed with water to afford the title compound (1.05 g, 16%) as a sandy tan solid. LC-MS (ES) m/z=275 [M+H]+.

Provenance & Evidence