Nonane → tert-Butyl [3-(4-{[(1-adamantylmethyl)amino]carbonyl)-5-chloropyridin-2-yl)propyl](3-{[tert-butyl(dimethyl)silyl]oxy}propyl)carbamate

Participants

Reaction Conditions

Reaction Steps

A solution of tert-butyl allyl(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)carbamate (0.50 g) in 9-boroabicyclo[3.3.1]nonane (6.0 ml of a 0.5M solution in tetrahydrofuran) was heated at reflux under nitrogen for 4 hours. The solution was cooled to 0° C. and potassium phosphate (2 ml of a 3M solution in water) was added. The mixture was stirred for 15 minutes and a solution of N-(1-adamantylmethyl)-2,5-dichloroisonicotinamide (0.50 g) (prepared as described in WO 01/94338) and tetrakis(triphenylphosphine)palladium (0) (0.045 g) in anhydrous N,N-dimethylformamide (3 ml) was added. The mixture was heated at 70° C. under nitrogen for 4 hours, diluted with saturated brine (25 ml) and extracted into ethyl acetate (3×25 ml). The combined extracts were dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by chromatography on silica, gel eluting with iso-hexane:ethyl acetate (9:1 to 4:1) to afford the sub-titled compound (0.46 g).

Provenance & Evidence