Cyanogen Bromide → HCID 86626298, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2-chloro-N4-[(1S)-1-phenylethyl]quinoline-3,4-diamine (13.0 g, 43.7 mmol) in ethanol (100 mL) was heated to 80° C. for 30 minutes. Cyanogen bromide (4.6 g, 44 mmol) was added, and the dark solution was heated at 80° C. for one hour. An analysis by LC/MS indicated the presence of starting material. Additional cyanogen bromide (4.6 g, 44 mmol) was added, and the reaction was stirred overnight at 80° C. The reaction was still incomplete, and additional cyanogen bromide (4.6 g, 44 mmol) was added. The reaction was heated overnight at 100° C. after a fourth equivalent of cyanogen bromide (4.6 g, 44 mmol) was added. The solvent was removed under reduced pressure, and aqueous sodium hydroxide (200 mL of 2 N) was slowly added to the resulting oil. The mixture was stirred for two hours at room temperature, and a precipitate formed, which was isolated by filtration. The solid was then purified by automated flash chromatography (silica cartridge, eluting with aqueous ammonium hydroxide:methanol:dichloromethane in a gradient from 0:0:100 to 0.3:4.7:95) to provide 9.4 g of 4-chloro-1-[(1S)-1-phenylethyl]-1H-imidazo[4,5-c]quinolin-2-amine hydrobromide as a brown solid. A portion of the product was purified again by automated flash chromatography (silica cartridge, eluting with aqueous ammonium hydroxide:methanol:dichloromethane in a gradient from 0:0:100 to 0.2:3.8:96) to provide a sample of the product as gray needles, mp 170-172° C.

Provenance & Evidence