Reaction Steps
(E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 157 mg, 0.45 mmol), 4-(3-amino-pyrazol-1-ylmethyl)-benzoic acid methyl ester (117 mg, 0.50 mmol) and N,N-diisopropylethylamine (237 μL, 1.36 mmol) were combined in methylene chloride (20 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (173 mg, 0.45 mmol) was added and the ice bath was removed. After stirring 2 h, the reaction mixture was evaporated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate solution (1 mL) and extracted with chloroform (2×3 mL). The combined organic phases were dried over sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes) to afford (E)-4-{3-[2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester (188 mg, 74%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C26H27ClN4O6S [M+] 558.13, found 559 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.63 (m, 4 H, 2×CH2), 1.85 (m, 4 H, 2×CH2), 3.29 (s, 3 H, SO2CH3), 3.92 (s, 3 H, CO2CH3), 4.86 (m, 1 H, OCH), 5.29 (s, 2H, NCH2), 6.79 (d, J=2.3 Hz, 1 H, Ar), 7.23 (d, J=8.3 Hz, 2 H, Ar), 7.40 (d, J=2.3 Hz, 1 H, Ar), 7.55 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.65 (d, Jm=1.5 Hz, 1 H, Ar), 8.02 (d, J=8.3 Hz, 2 H, Ar), 8.18 (d, Jo=8.2 Hz, 1 H, Ar), 9.20 (s, 1 H, NH).
