1-Methylimidazole → HCID 86716074, compound

Participants

Reaction Conditions

Reaction Steps

n-BuLi (1.6 M in hexane, 3.65 mL, 5.84 mmol) was added to a solution of 1-methylimidazole (0.452 mL, 5.7 mmol) in THF (30 mL) at −78° C. The mixture was stirred at −78° C. for 15 min. Chlorotriethylsilane (0.955 mL, 5.7 mmol) was added slowly. The mixture was removed from the dry ice/acetone bath and was stirred for 30 min. The mixture was again cooled in a dry ice/acetone bath before addition of a second portion of n-BuLi (1.6 M in hexane, 3.65 mL, 5.84 mmol). The mixture was stirred at −78° C. for 1 hour, then transferred to an ice bath and stirred 10 min. The mixture was again cooled in a dry ice/acetone bath before addition of a solution of N-methoxy-N-methylpyridazine-4-carboxamide (793 mg, 4.74 mmol, Intermediate 29, step a) in THF (15 mL) via cannula. The reaction mixture was stirred at −78° C. for 30 min, then was transferred to a slurry of CH3CN/dry ice and stirred for 15 min. The reaction was quenched by addition of water (50 mL) and the mixture was extracted with EtOAc three times. The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 0-4% MeOH-DCM first column, 75-100% EtOAc-heptanes second column) to afford the title compound.

Provenance & Evidence