Cesium carbonate → 6-Cyclopropylmethoxy-5-(3-hydroxy-azetidin-1-yl)-pyridine-2-carboxylic acid [1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide

Participants

Reaction Conditions

Reaction Steps

5-Bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide (150 mg, 380 μmol) was dissolved in toluene (6.0 mL) to give a colorless solution. This solution was degassed under an Argon stream for 5 minutes. Cesium carbonate (371 mg, 1.14 mmol), Pd2(dba)3CHCl3 (39.3 mg, 38.0 μmol), [rac]-BINAP (47.3 mg, 75.9 μmol) and 3-azetidinol hydrochloride (1:1) (CAN 18621-18-6; 49.9 mg, 455 μmol) were added and the mixture was heated for 18 hours in a microwave oven to 100° C. After cooling to room temperature the mixture was diluted with ethyl acetate (5 mL) and water (3 mL), filtered through Celite® and the filter pad was washed with water (10 mL) and ethyl acetate (30 mL). Phases were separated and the aqueous phase was extracted with ethyl acetate (20 mL). Organic phases were combined, dried with Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography (silica gel. 20 g, 0% to 100% ethyl acetate in heptane) to give the title compound (80 mg, 54%) as yellow solid; NMR complies.

Provenance & Evidence