2,6-Lutidine → N-(1-Carbamoylmethyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Participants

Reaction Conditions

Reaction Steps

To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (166 μL, 0.33 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (46 μL, 0.39 mmol) was added to the solution at 0° C. After 1 h, the crude 2-(3-amino-pyrazol-1-yl)-acetamide (0.30 mmol based on theory) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford N-(1-Carbamoylmethyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (38 mg, 28%) as a white solid: ESI-LRMS m/e calcd for C20H25ClN4O4S [M+] 452.13, found 453.2 [M+H+]; 1H NMR (400 MHz, CD3OD) δ ppm 1.11-1.27 (m, 2H, CH2), 1.46-1.92 (m, 8H, 4×CH2), 2.07-2.27 (m, 1H, CH), 3.28 (s, 3H, SO2CH3), 3.85 (dd, J=8.6, 6.4 Hz, 1H, CH), 4.73 (s, 2H, NCH2), 6.55 (d, J=2.4 Hz, 1H, Ar), 7.53 (d, J=2.4 Hz, 1H, Ar), 7.59 (dd, Jo=8.2, Jm=1.5 Hz. 1H, Ar), 7.71 (d, Jm=1.5 Hz, 1H, Ar), 8.05 (d, Jo=8.2 Hz, 1H, Ar).

Provenance & Evidence