Trifluoroacetic acid → HCID 10167188, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 176 mg (0.55 mmol) of 4-(benzo[d]isoxazol-3-yloxy)-piperidine-1-carboxylic acid tert-butyl ester in CH2Cl2(2 mL) was treated with trifluoroacetic acid (0.5 mL) at room temperature overnight. The solvent was then removed and the crude product dissolved in methanol and stirred over 100 mg of sodium bicarbonate for 1 h, the solid was then filtered off and the filtrate concentrated. The crude piperidine was then dissolved in 4 mL EtOH and treated with 202 mg (0.55 mmol) of 1-[1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone The solution was heated to 60° C. overnight. The solvent was then removed by rotary evaporation and the crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc) to afford 220 mg (68%) of a white solid. MS (electrospray): exact mass calculated for C30H32F3N5O4, 583.24; m/z found, 584.2 [M+H]+. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers): 7.77 (d, J=8.22 Hz, 1H), 7.69 (m, 2H), 7.66-7.61 (m, 2H), 7.54-7.49 (m, 1H), 7.41 (d, J=8.41 Hz, 1H), 7.28-7.23 (m, 1H), 4.93 (br m, 1H), 4.88 and 4.75 (A and B of AB quartet, J=15.65 Hz, 1H), 4.65 (br s, 1H), 4.24-4.18 (m, 0.75H), 4.18-4.09 (m, 1.25H), 4.07-3.98 (m, 1.5H), 3.91-3.79 (m, 0.5H), 3.79-3.67 (m, 1H), 3.02-2.85 (m, 2.4H), 2.85-2.70 (m, 1.6H), 2.61-2.52 (m, 1H), 2.51-2.40 (m, 2H), 2.39-2.30 (m, 1H), 2.24-2.12 (br m, 2H), 2.20 (s, 1.5H), 2.16 (s, 1.5H), 2.02-1.86 (m, 2H).

Provenance & Evidence