Lithium Hydroxide → [6-(3,5-Dimethyl-isoxazol-4-yl)-1H-imidazo[4,5-b]pyridin-2-ylmethyl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a dry 20 mL microwave vessel equipped with a stir bar, 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (125 mg, 0.153 mmol) and LiOH (110 mg, 4.58 mmol) were combined. The vessel was capped with septa and purged three times with vacuum and nitrogen. The mixture was suspended into degassed, 10:1 dioxane: H2O (2.5 mL). To the suspension, (6-Bromo-1H-imidazo[4,5-b]pyridin-2-ylmethyl)-carbamic acid tert-butyl ester (500 mg, 1.528 mmol), 3,5-dimethylisoxazole-4-boronic acid (323 mg, 2.292 mmol) and pinacol (271 mg, 2.292 mmol) were added. The reaction mixture was purged again with vacuum and nitrogen three times and sealed using a microwave crimped septa. The reaction vessel was placed in a microwave reactor and heated at 120° C. for 2.5 hrs. The reaction was complete based on LC/MS (M+1=344). The resulting brown suspension was concentrated under reduced pressure to dryness and reconstituted with 20 mL of 10% MeOH-DCM. 30 g of 230-400 mesh SiO2 was then added and the resulting slurry was stirred vigorously. Removed solvent under reduced pressure and packed compound absorbed on silica into a 40 g SIM cartridge. Purified crude using SiO2 flash chromatography (120 g ISCO cartridge; 230-400 mesh SiO2) equilibrated with 10% MeOH-DCM containing 0.5% triethylamine to give 360 mg of the title compound as an amber oil (69%).

Provenance & Evidence