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

Participants

Reaction Conditions

Reaction Steps

2(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 175 mg, 0.53 mmol) was dissolved in methylene chloride and a 2.0 M solution of oxalyl chloride in methylene chloride (193 mg, 0.58 mmol) was added. The reaction stirred at 25° C. for 1 h. The reaction was chilled to 0° C. under nitrogen and 2,6-lutidine (142 μL, 1.22 mmol) was added dropwise. The reaction became golden brown, the ice bath was removed and the reaction continued to stir at 25° C. for 30 min. 1-Ethyl-1H-pyrazol-3-ylamine (59 mg, 0.51 mmol) was dissolved in methylene chloride and added dropwise to the reaction. The solution continued to stir at 25° C. for 16 h. The reaction was diluted with methylene chloride, washed with water and saturated aqueous brine solution. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 40 g; 10% ethyl acetate/hexanes to 70% ethyl acetate/hexanes) afforded 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-ethyl-1H-pyrazol-3-yl)-propionamide as a white powder (139 mg, 62%) ESI-LRMS m/e calcd for C20H26ClN3O3S [M+] 423.1, found 424.1 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.07-1.21 (m, 2H, CH2), 1.44 (t, J=7.3 Hz, 3H, CH3), 1.47-1.96 (m, 8H, 4×CH2), 2.16-2.29 (m, 1H, CH), 3.26 (s, 3H, SO2CH3), 3.53 (t, J=7.5 Hz, 1H, CH), 4.03 (q, J=7.3 Hz, 2H, NCH2), 6.64 (d, J=2.3 Hz, 1H, Ar), 7.27 (d, J=2.3 Hz, 1H, Ar), 7.46 (dd, Jo=8.1, Jm=1.7 Hz. 1H, Ar), 7.59 (d, Jm=1.7 Hz, 1H, Ar), 7.94 (s, 1H, NH), 8.08 (d, Jo=8.1 Hz, 1H, Ar).

Provenance & Evidence