Cesium carbonate → 5-(3,3-Difluoro-azetidin-1-yl)-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [1-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [1-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide (Example 78g, 0.05 g, 111 μmol) in dry Toluene (1 ml) under argon atmosphere were added palladium(II) acetate (3.75 mg, 16.7 μmol), BINAP (10.4 mg, 16.7 μmol), cesium carbonate (90.7 mg, 278 μmol) and 3,3-difluoroazetidine hydrochloride (CAN 288315-03-7, 15.9 mg, 122 μmol). The reaction mixture was stirred at 120° C. for 45 minutes under microwave radiation. The reaction mixture was filtered through a pad of Celite and the filtrate was concentrated in vacuo. The residue was dissolved in ethylacetate and extracted with an 1.0M aqueous solution of sodium bicarbonate. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient to yield the title compound (14.2 mg, 28%) as a white solid. MS (ESI, m/z): 462.4 (M+H+).

Provenance & Evidence