Dimethylformamide → [3-(2-tert-Butyl-pyrimidin-4-yl)-6-chloro-1H-indol-5-yl]-[4-(4-fluorobenzyl)-piperidin-1-yl]-methanone

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-Acetyl-6-chloro-5-[4-(4-fluoro-benzyl)-piperidine-1-carbonyl]-indole-1-carboxylic acid benzyl ester (150 mg, 0.27 mmol) in N,N-dimethylformamide (1 mL) was added dimethylformamide (N,N)-di-tert-butyl acetal (0.5 mL, 2.1 mmol) and the solution was heated to 75° C. for 5 h. The material was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. This material was filtered and concentrated to give an orange oil. This was dissolved in N,N-dimethylformamide (1 mL), added 2,2,2-trimethylacetamidine hydrochloride 85° C. for 18 h. The slurry was cooled to ambient temp and partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The material was filtered and concentrated to an orange oil and purified by silica gel chromatography using ethyl acetate/heptane to afford the title compound as a yellow semi-solid (12.1 mg, 9%). MH+, m/z=505.

Provenance & Evidence