Diisopropylethylamine → 4-(1-(2-Chloro-6-methylphenylsulfonyl)piperidin-2-yl)-1-(4-(pyridin-3-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidin-1-yl)butan-1-one

Participants

Reaction Conditions

Reaction Steps

1-Hydroxybenzotriazole hydrate (HOBT) (0.022 g, 0.168 mmol, 0.3 eq.) and N-ethyl-diisopropylamine (0.285 ml, 1.68 mmol, 3 eq.) were added to a solution of 4-(1-(2-chloro-6-methylphenylsulfonyl)piperidin-2-yl)butanoic acid (0.252 g, 0.7 mmol, 1.25 eq.) in methylene chloride (7 ml). The mixture was cooled to 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) (0.161 g, 0.84 mmol, 1.5 eq.) was added and the mixture was stirred for 15 min. 3-(4-(2-(Pyrrolidin-1-yl)ethoxy)piperidin-4-yl)pyridine dihydrochloride (0.195 g, 0.56 mmol, 1 eq.) was then added. The reaction mixture was stirred at room temperature for 72 h. For working up, sat. sodium bicarbonate solution was added to the mixture and the mixture was diluted with ethyl acetate. The phases were separated, and the aqueous phase was extracted 2× with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography [Alox Neutral (25 g), ethyl acetate 100%→ethyl acetate/methanol 95:5]. The desired product was obtained as a yellow-white solid in a yield of 61% (0.212 g).

Provenance & Evidence