1-Hydroxybenzotriazole → 2-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-1-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethoxy)-azepan-1-yl]-ethanone

Participants

Reaction Steps

DIPEA (2.5 eq.) was added to a cooled solution (0° C.) of (S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid [acid D] in methylene chloride (5 ml/mmol), followed by HOBt (1 eq.) and EDCl (1.5 eq.). The reaction mixture was stirred at room temperature for 10 min and cooled to 0° C. and 4-(pyridin-3-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)azepan hydrochloride [amine K] (1.2 eq.) was added. The reaction mixture was then stirred at room temperature for 16 h. In this time, the educts reacted completely (TLC control). The reaction mixture was diluted with methylene chloride (20 ml) and washed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and finally with sat. sodium chloride solution again. The organic phase was dried over sodium sulfate and concentrated to dryness on a rotary evaporator. The crude product was purified by means of column chromatography (silica gel, 2% methanol in methylene chloride). Yield: 46%. MS, Rt=2.8 min, m/z=643.4 [MH]+

Provenance & Evidence