Hydrochloric Acid → benzyl N-(1-methyl-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl)carbamate

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Reaction Steps

Combine benzyl N-[(3R)-2-methylsulfanyl-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate (500 mg, 1.47 mmol), propargylamine (197.28 μL, 2.94 mmol), and p-toluenesulfonic acid monohydrate (30 mg, 157.71 μmoles) in phenyl ether-biphenyl mixture (2 mL, 6.53 mmol) (Dowtherm A) and stir the mixture for approximately 45 minutes at 180° C. Cool the reaction, and add ether (20 mL), then 2M HCl (20 mL). Stir for a few minutes, remove the aqueous layer, and extract the organic layer with 2N HCl (2×). Combine the aqueous layers and basify with ammonium hydroxide (28%) until alkaline. Collect the precipitate by filtration, wash it with water, and dry it in a vacuum oven. Purify the precipitate by flash chromatography (50% of a 5% solution of ammonia/methanol (2M) in dichloromethane to 90% of the 5% solution) to give the title compound (358 mg, 70%) as an off white solid: MS (m/z): 348 (M+1). Retention time for Isomer 1 (S Isomer)=3.3 min; Isomer 2 (R Isomer)=3.7 min. (Chiralpak AD-H column; 100% EtOH with 0.2% dimethylethylamine; flow rate 1.0 mL/min; 225 nM). Chiral analysis indicates about 20% racemization.

Provenance & Evidence