Dimethylformamide → ethyl 2-(3-cyano-2-cyclopentyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate

Participants

Reaction Steps

To a solution of ethyl 2-(5-cyclopentyl-2-methyl-3-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (2.54 g, 5.54 mmol) in acetonitrile (28 mL) was added chlorosulfonyl isocyanate (0.818 ml, 9.42 mmol). The reaction was stirred at room temperature for 30 minutes, after which the starting pyrrole had still not been consumed. The reaction was then heated to 55° C. for 30 minutes after which the starting pyrrole was consumed (by LCMS analysis). To the reaction mixture at 55° C. was added N,N-dimethylformamide (0.729 ml, 9.42 mmol). The reaction was stirred at 55° C. for 30 minutes after which analysis of the reaction (by LCMS) indicated that the reaction to afford the desired product was complete. The reaction was quenched by the addition of water, and extracted with dichloromethane (3×50 mL), dried (sodium sulfate), filtered and concentrated to a deep maroon residue. Purification was achieved by silica gel chromatography (Luknova 240 g, 20 mL/min) using 1 to 7% of a 7:1 acetonitrile/methanol solution in dichloromethane over 70 minutes. The product ethyl 2-(3-cyano-2-cyclopentyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (747 mg, 1.55 mmol, 28% yield) was isolated as a white foam. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.01 (d, 1H), 7.40 (dd, 1H), 7.30 (ddd, 1H), 6.99 (d, 1H), 4.59 (s, 2H), 4.30 (s, 2H), 4.27 (q, 2H), 3.32-3.36 (m, 4H), 2.96 (m, 1H), 1.84-2.09 (m, 13H, composite of multiple shifts), 1.63-1.71 (m, 2H).

Provenance & Evidence