Reaction Steps
A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-furan-3-yl)-propionic acid (100 mg, 0.30 mmol) in methylene chloride (8 mL) was cooled to 0° C. To this solution was then added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 180 μL, 0.36 mmol) and N,N-dimethylfomamide (two drops) which produced gas evolution and it was then stirred at 0° C. for 20 minutes and 40 min at 25° C. After this time, the reaction was concentrated in vacuo and azeotroped with methylene chloride (10 ml). In a separate flask a solution of 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-ylamine (prepared in Example 67, 80 mg, 0.33 mmol), 2,6-lutidine (52 μL, 0.45 mmol) in methylene chloride (6 mL) was cooled to 0° C. in an ice bath. To this solution was then dropwise the solution of the prepared acid chloride diluted with another portion of methylene chloride (6 mL). After addition was complete, the reaction was stirred at 0° C. for 15 min and at 25° C. for 3 hours. After this time it was concentrated in vacuo and purified on an AnaLogix Intelliflash system (40 g column, 30% ethyl acetate/hexanes to 60% ethyl acetate/hexanes) to afford N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-furan-3-yl)-propionamide (138 mg, 86%) as a clear colorless oil: 1H NMR (300 MHz, DMSO-d6) δ ppm −0.09-0.06 (2×s, 6H, 2×SiCH3), 0.77, 0.82 (2×s, 9H, 3×CH3), 1.44-1.57 (m, 1H, CH of CH2), 1.70-2.22 (m, 4H, CH and 3×CH of 2×CH2), 3.22-3.29 (m, 1H, OCH of OCH2), 3.33, 3.34 (2×s, 3H, SO2CH3), 3.51-3.63 (m, 1H, OCH of OCH2), 3.66-3.94 (m, 5H, ArCH, SiOCH2, and 2×OCH of 2×OCH2), 4.01-4.08 (m, 2H, NCH2), 6.41 (d, J=2.2 Hz, 1H, Ar), 7.53 (d, J=2.2 Hz, 1H, Ar), 7.60 (2×dd, Jo=8.2 Hz, Jm=1.6 Hz, 1H, Ar), 7.71 (2×d, Jm=1.6 Hz, 1H, Ar), 8.01 (d, Jo=8.2 Hz, 1H, Ar), 10.82, 10.83 (2×s, 1H, NH).
