In a round bottom flask was added 6-(4-amino-2-methylphenyl)-4-(4-hydroxy-3-methylphenyl)pyrimidin-2(1H)-one (3) (30 mg, 0.10 mmol), 1,2 dichloroethane (2.0 mL), acetic acid (0.1 mL), and commercially available N-Boc-4-formyl piperidine (29 uL, 0.14 mmol). The reaction was stirred at room temperature for 15 minutes before adding sodium triacetoxy borohydride (30 mg, 0.14 mmol). Stirring was continued at room temperature overnight. The reaction was then quenched with saturated NaHCO3, extracted with EtOAc, dried over Na2SO4 and concentrated to dryness. The resultant oil was then dissolved in 4N HCl/dioxane (1.0 mL) and allowed to sit at RT for 30 min. or until Boc deprotection was complete. The 4N HCl/dioxane was decanted, and the residual solid product was rinsed with EtOAc 4×. The resulting orange solid was then dissolved in MeOH and purified by preparatory HPLC (5-85% gradient of AmAc/ACN, 15 min.) to give the product 4-(4-hydroxy-3-methylphenyl)-6-{2-methyl-4-[(piperidin-4 ylmethyl)amino]phenyl}pyrimidin-2(1H)-one as the acetate salt after lyopholyzation (24 mg, 59% yield).
