Acetic Acid → 1-(4-(5-(1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

Participants

Reaction Steps

To a solution of 4-(5-(1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (1.0 g, 2.60 mmol) in DCM (10 mL) was added acetic acid (15 mL) and azetidine-3-carboxylic acid (1.5 eq, 3.90 mmol). The mixture was stirred at RT for 40 min., then a suspension of sodium triacetoxyborohydride (1 eq, 2.60 mmol) in DCM (30 mL) was added dropwise over 1.5 h. The volatiles were removed in vacuo, water (200 mL) was added and the resulting solid was collected by filtration. Ethyl acetate (40 mL) was added to the crude product and after sonication for 30 min, the solids were collected by filtration and washed additional ethyl acetate to afford 1-(4-(5-(1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzyl) azetidine-3-carboxylic acid (777 mg, 1.65 mmol) as a white solid. The compound had an HPLC retention time=2.55 min. Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.2% H3PO4; Solvent B=90% MeOH, 10% H2O, 0.2% H3PO4. LC/MS M+1=471.05. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.21-3.25 (m, 3H), 3.40-3.44 (m, 2H), 3.64 (s, 2H), 7.51 (d, J=8.3 Hz, 2H), 7.69 (ddd, J=0.8 Hz, 4.7 Hz, 8.3 Hz, 1H), 7.90 (d, J=8.0 Hz, 1H), 8.03 (d, J=8.3 Hz, 2H), 8.20 (dt, J=1.9 Hz, 7.7 Hz, 1H), 8.66 (dd, J=1.1 Hz, 4.1 Hz, 1 H) 8.73 (s, 1H).

Provenance & Evidence