Diisopropylethylamine → N-[1-(2,3-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-3-[5-(4-methoxyphenyl)pyrimidin-2-yl]propionamide Hydrochloride Salt

Participants

Reaction Steps

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.29 g, 1.5 mmol, 1.5 equiv.) was added to a suspension of 3-[4-(4-methoxyphenyl)pyrimidin-2-yl]-propanoic acid (0.26 g, 1.0 mmol, 1.0 equiv.), 3-(RS)-aminomethyl-1-(2,3-dichlorobenzyl)-pyrrolidine (0.26 g, 1.0 mmol), 1-hydroxybenzotriazole hydrate (0.20 g, 1.5 mmol, 1.5 equiv.), and diisopropylethylamine (0.44 mL, 2.5 mmol, 2.5 equiv.) in chloroform (2 mL). After stirring overnight at room temperature, the reaction mixture was diluted with ethyl acetate, washed sequentially with 1 M sodium hydroxide, water, 1 M hydrochloric acid, water and brine, then dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (0→10% methanol in methylene chloride). Clean fractions containing the desired product were combined and concentrated, diluted with dioxane and treated with 4 M HCl (0.2 mL) in dioxane. The solution was concentrated under high vacuum to give N-(1-(2,3-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl)-3-(5-(4-methoxyphenyl)pyrimidin-2-yl)propionamide as the HCl salt (185 mg).

Provenance & Evidence