Reaction Steps
Triphenylphosphine (224 mg, 0.85 mmol) was dissolved in methylene chloride (3 mL) and cooled to 0° C. To this solution was added N-bromosuccinimide (172 mg, 0.97 mmol) and was stirred at 0° C. until it was completely dissolved and became light purple in color. The 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1; 188 mg, 0.57 mmol) was then added and it was stirred at 0° C. for 20 min and then warmed to 25° C. and stirred for another 30 min. After such time 1-(3-methyl-but-2-enyl)-1H-pyrazol-3-ylamine (86 mg, 0.57 mmol) and 2,6-lutidine (198 μL, 1.71 mmol) were added and the reaction was stirred at 25° C. for 16 h. The reaction was then diluted with ethyl acetate (50 mL), washed with water (2×15 mL), saturated aqueous brine solution (1×15 mL), dried over magnesium sulfate and concentrated in vacuo to give an orange oil. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 20% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) followed by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% ethyl acetate/methylene chloride to 20% ethyl acetate/methylene chloride) afforded 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-methyl-but-2-enyl)-1H-pyrazol-3-yl]-propionamide (103 mg 39%) as an off white powder: ESI-LRMS m/e calcd for C23H30ClN3O3S [M+] 463.17, found 464.23 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.23 (m, 2H, CH2), 1.46-1.93 (m, 8H, 4×CH2), 1.76 (s, 3H, CH3), 1.80 (s, 3H, CH3), 2.05-2.35 (m, 1H, CH), 3.28 (s, 3H, SO2CH3), 3.53 (t, J=7.6 Hz, 1H, CH), 4.59 (d, J=7.1 Hz, 2H, NCH2), 531-5.43 (m, 1H, vinylic), 6.66 (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), 7.83 (s, 1H, NH), 8.10 (d, Jo=8.1 Hz, 1H, Ar).
