Nonane → N-(1-Adamantylmethyl)-5-chloro-2-[3-(ethylamino)propyl]isonicotinamide hydrochloride

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Reaction Steps

A solution of tert-butyl allylcarbamate (Example 7(iv)) (0.23 g) in 9-boroabicyclo[3.3.1]nonane (5 ml of a 0.5M solution in tetrahydrofuran) was heated at reflux under nitrogen for 6 hours. The solution was cooled to room temperature and potassium phosphate (1 ml of a 3M solution in water) was added. The mixture was stirred for 15 minutes and a solution of N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide (Example 1(ii)) (0.383 g) and dichloro[1,1′-bis(diphenylphosphino)ferrocenyl]palladium (II) (0.045 g) in anhydrous N,N-dimethylformamide (8 ml) was added. The mixture was stirred for 6 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 (4:1 to 2:1). The isolated material (0.30 g) was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and concentrated; the resultant solid was triturated with ethyl acetate and the solid collected by filtration to afford the titled compound (0.245 g) as a colourless powder.

Provenance & Evidence