Water → (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask was placed (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide (85 mg, 0.15 mmol), tetrahydrofuran (2 mL), water (0.5 mL) and acetic acid (2 mL). This solution was then stirred at 25° C. until all starting material is consumed (˜4 hr). The reaction was then diluted with water (10 mL) and transferred to a separatory funnel where it was extracted with ethyl acetate (3×10 mL). The organic layers were combined and then washed with saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 100% ethyl acetate to 5% methanol/ethyl acetate) afforded (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide (67 mg, 99%) as a white foam: [α]29589=−11.5° (c=0.13, methylene chloride); ES-HRMS m/e calcd for C20H24N3O5SCl (M+H)+ 454.1198, observed 454.1193; 1H NMR (300 MHz, DMSO-d6) δ 1.51 (m, 1H, CH), 1.78-2.30 (m, 8H, 4×CH2), 3.34 (s, 3H, SO2CH3), 3.67 (q, J=5.4 Hz, 2H, OCH2), 3.96 (m, 1H, ArCHCO), 4.00 (m, 2H, NCH2), 4.84 (t, J=5.4 Hz, 1H, OH), 6.41 (d, J=2.1 Hz, 1H, Ar), 7.55 (d, J=2.1 Hz, 1H, Ar), 7.62 (d, Jo=8.3 Hz, 1H, Ar), 7.73 (s, 1H, Ar), 8.02 (d, Jo=8.3 Hz, 1H, Ar), 10.85 (s, 1H, NH).

Provenance & Evidence