Ammonia → HCID 16035375, compound

Participants

Reaction Steps

A solution of dimethyl sulfoxide (0.10 g) in dichloromethane (1 mL) was added to oxalyl chloride (0.083 g) in dichloromethane (10 mL) at −78° C. The reaction was stirred for 15 minutes and then a solution of N-(2-diethylaminoethyl)-N-(2-hydroxyethyl)-3-phenethyloxy-propanamide (Example 12a), 0.20 g) in dichloromethane (1 mL+1 mL wash) was added and the reaction mixture was stirred for a further 15 minutes. Triethylamine (0.30 g) was added and the reaction mixture was allowed to warm to room temperature over 1 hour. The mixture was subsequently diluted (dichloromethane, 30 mL), the organics washed with saturated sodium hydrogencarbonate solution (20 mL) and then brine (20 mL), dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give a crude aldehyde product which was used immediately. The crude product was dissolved in methanol (10 mL) and 7-(2-aminoethyl)-4-hydroxy-3H-benzothiazol-2-one hydrochloride (0.15 g) added along with acetic acid (0.1 mL) and water (0.1 mL). After stirring at room temperature for 30 minutes, sodium cyanoborohydride (0.022 g) was added and the reaction mixture was stirred overnight. Ammonia (7N in methanol, 1 mL) was added and the mixture was concentrated. The crude residue was purified by flash silica column chromatography eluting with 1% ammonia; 5%-7% methanol in dichloromethane. The isolated product was dissolved in dichloromethane and treated with 4 N hydrogen chloride in 1,4-dioxane (0.5 mL) and concentrated. The oily residue was triturated with ether, decanting the ether and concentrating to afford the titled compound as a white solid (0.032 g).

Provenance & Evidence