3-Pyridinecarboxaldehyde → N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-N-[2-{1-[(pyridin-3-ylmethyl)amino]propyl}-5-(trifluoromethyl)benzyl]-2H-tetrazol-5-amine

Participants

Reaction Steps

To a solution of N-[2-(1-aminopropyl)-5-(trifluoromethyl)benzyl]-N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-2H-tetrazol-5-amine (60.0 mg, 0.01 mmoles) in ethanol (0.85 mL) was added 3-pyridinecarboxaldehyde (26.0 mg, 0.122 mmoles) and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was cooled to 0° C. and sodium borohydride (10.0 mg, 0.133 mmoles) was added in one portion. The reaction mixture was stirred in ice bath for 2 hours and then at room temperature for overnight. The reaction mixture was concentrated to remove ethanol and the residue was taken up in ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×) and the combined organic layer was washed with brine, dried over sodium sulfate and concentrated. The crude product was purified using silica gel chromatography on the ISCO Combiflash system with a 1-9% methanol in dichloromethane gradient to yield the title compound (54.6 mg, 78% yield) as colorless gum.

Provenance & Evidence