Potassium Iodide → Ammonia

Participants

Reaction Conditions

Reaction Steps

N-{2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}formamide (Prepared according to US2005/215590, 500 mg, 1.1 mmol), 4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol bis hydrochloride salt (Preparation 13, 745 mg, 1.3 mmol), sodium hydrogen carbonate (550 mg, 6.5 mmol) and potassium iodide (50 mg, 0.30 mmol) were added to propionitrile (8 ml) and heated to 90° C. and left to stir overnight. Further 4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol (Preparation 13, 50 mg, 0.087 mmol) was then added and mixture stirred at 90° C. for further 24 hours. After cooling, ethyl acetate and saturated aqueous sodium hydrogen carbonate were added, organics separated and washed with more saturated aqueous sodium hydrogen carbonate, then brine and then dried (magnesium sulphate) and solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (96:4:0.4 to 92:8:0.8 by volume) to furnish the title compound as an oil, 400 mg.

Provenance & Evidence