3,5-Dimethylpyrazole → 6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-3-(3,5-dimethyl-1H-pyrazol-1-yl)-7-fluoro-1,2-benzoxazole-5-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a stirred and degassed solution of 3-chloro-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde (Intermediate 534, 0.15 g, 0.48 mmol) in toluene was added K3PO4 (0.51 g, 2.40 mmol), 3,5-dimethyl-1H-pyrazole (92 mg, 0.96 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-phos) (4 mg, 0.009 mmol) and tris(dibenzylideneacetone) dipalladium(0) (8 mg, 0.009 mmol), sequentially and the reaction mixture was heated to 150° C. for 2 h in microwave reactor. The reaction mixture was diluted with EtOAc (15 mL). The organic layer was washed successively with water (2×10 mL), brine (2×10 mL), dried over anhydrous Na2SO4 and, after filtration, concentrated. The residue was purified over silica gel column using a gradient of ethylacetate in pet.ether to give product title compound as solid. Yield: 100 mg (56%).

Provenance & Evidence