2,6-Lutidine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-hydroxy-propyl)-1H-pyrazol-3-yl]-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 (181 μL, 0.36 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (70 μL, 0.61 mmol) was added to the solution at 0° C. After 1 h, 3-(3-amino-pyrazol-1-yl)-propan-1-ol (0.42 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 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-hydroxy-propyl)-1H-pyrazol-3-yl]-propionamide (47 mg, 34%) as a white solid: ESI-LRMS m/e calcd for C21H28ClN3O4S [M+] 453.15, found 454.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.02-1.21 (m, 2H, CH2), 1.40-1.92 (m, 8H, 4×CH2), 1.92-2.02 (m, 2H, CH2), 2.11-2.28 (m, 1H, CH), 2.88 (brs, 1H, OH), 3.26 (s, 3H, SO2CH3), 3.50-3.67 (m, 3H, OCH2 and CH), 4.11 (t, J=6.4 Hz, 2H, NCH2), 6.63 (d, Jo=2.3, 1H, Ar), 7.26 (d, Jo=2.3, 1H, Ar), 7.45 (dd, Jo=8.2, Jm=1.6 Hz. 1H, Ar), 7.58 (d, Jm=1.6 Hz, 1H, Ar), 8.05 (d, Jo=8.2 Hz, 1H, Ar), 8.38 (s, 1H, NH).

Provenance & Evidence