Acetic Anhydride → (αR)-N-[1-[2-(Acetyloxy)ethyl]-1H-pyrazol-3-yl]-3-chloro-α-(cyclopentylmethyl)-4-(methylsulfonyl)benzeneacetamide

Participants

Reaction Conditions

Reaction Steps

2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamide (prepared in Example 67, 102 mg, 0.27 mmol) was dissolved in pyridine (2 mL) and acetic anhydride (27 umL, 0.29 mmol) was added. The reaction stirred at 25° C. for 16 h. The solution was diluted with ethyl acetate (40 mL), washed with aqueous 1.0 M hydrochloric acid solution (3×15 mL), saturated aqueous brine solution (1×10 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) afforded acetic acid 2-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-ethyl ester (78 mg, 60%) as a white foam: ESI-LRMS m/e calcd for C22H28ClN3O5S [M+] 481.1, found 482.3 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.20 (m, 2 H, CH2), 1.39-1.79 (m, 8H, 4×CH2), 1.95 (s, 3H, COCH3), 2.01-2.19 (m, 1H, CH), 3.33 (s, 3H, SO2CH3), 3.86-3.95 (m, 1H, CH), 4.18-4.24 (m, 2H, OCH2), 4.29 (t, J=5.0 Hz, Hz, 2H, NCH2), 6.43 (d, Jo=2.3 Hz, 1H, Ar), 7.55-7.61 (m, 2H, Ar), 7.68 (d, Jm=1.7 Hz, 1H, Ar), 7.99 (d, Jo=8.2 Hz, 1H, Ar), 10.77 (s, 1H, NH).

Provenance & Evidence