Diisopropylcarbodiimide → HCID 136078764, compound

Participants

Reaction Steps

To a solution of 3-(1-(3,5-difluorophenyl)cyclohexyl)propanoic acid (20 mg, 0.075 mmol) and (Z)—N′-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine-3-carboximidamide (12.46 mg, 0.075 mmol) in acetonitrile (1 mL) was added N,N′-diisopropylcarbodiimide (0.013 mL, 0.082 mmol), and the mixture was stirred for 2.5 hrs at room temp. TBAF (0.112 mL, 0.112 mmol) was added and the mixture was stirred at room temperature. The oxadiazole formation was very slow. After 1 day of stirring, an additional 0.112 mL of 1M TBAF was added and the mixture was stirred for 5 more days. The mixture was diluted with EtOAc and washed with water and brine. The organic extract was dried over Na2SO4 and evaporated to give an oily residue which was purified by Combiflash (12 g silica gel). Elution with 7:93 MeOH—CH2Cl2 afforded a white solid which was repurified by prep HPLC to give pure 3-(5-(2-(1-(3,5-difluorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)-6-methylpyridin-2(1H)-one (8.0 mg, 26.7% yield) as a white solid. HPLC: tR=3.95 min, Waters Sunfire C18 4.6×50 mm, 4 min gradient, Detection Wave length 220 nm, Starting solvent: 10% aq. MeOH-0.1% TFA; Final solvent: 90% aq. MeOH-0.1% TFA. LC/MS: m/e 400.12 (M+H)+. 1H NMR (400 MHz, CDCl3): δ ppm 8.19 (1 H, d), 6.84-6.86 (2 H, m), 6.65 (1H, m), 6.21 (1H, d), 2.44-2.54 (5 H, m), 2.04-2.06 (4 H, m), 1.39-1.61 (8 H, m).

Provenance & Evidence