Methyl iodide → HCID 57785965, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 1-(4-bromo-2-chlorophenyl)-9-chloro-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (200.0 mg, 0.439 mmol) in N,N-dimethylformamide (2.0 mL) were added copper(I) iodide (125.5 mg, 0.659 mmol) and sodium methoxide (28% wt methanol solution, 1.0 mL). The reaction mixture was stirred at 100° C. for 10 hrs. After cooling, the mixture was filtered through on the pad of celite. The filtrate was diluted with water and extracted with ethyl acetate (×1). The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude product was subject to next step without further purification. The resulting carboxylic acid was dissolved into N,N-dimethylformamide (3.0 mL) and to the mixture were added potassium carbonate (130.9 mg, 0.947 mmol) and methyl iodide (88.5 μL, 1.422 mmol) at 0° C. The reaction mixture was stirred at room temperature for 16.5 hrs. The mixture was quenched with aqueous saturated ammonium chloride and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-35% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless amorphous (121.8 mg, 0.300 mmol, 68% (2 steps)).

Provenance & Evidence