Reaction Steps
(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 100 mg, 0.29 mmol), N-[3-(3-amino-pyrazol-1-ylmethyl)-phenyl]-acetamide (67 mg, 0.29 mmol) and N,N-diisopropylethylamine (151 μL, 0.87 mmol) were combined in methylene chloride (1.5 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (110 mg, 0.29 mmol) was added and the ice bath was removed. 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/chloroform to 80% ethyl acetate/hexanes) to afford (E)-N-[1-(3-acetylamino-benzyl)-1H-pyrazol-3-yl]-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetamide (67 mg, 42%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C26H28ClN5O5S [M+] 557.15, found 558 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.63 (m, 4 H, 2×CH2), 1.84 (m, 4 H, 2×CH2), 2.16 (s, 3 H, CO2CH3), 3.29 (s, 3 H, SO2CH3), 4.86 (m, 1 H, OCH), 5.20 (s, 2H, NCH2), 6.75 (d, J=2.3 Hz, 1 H, Ar), 6.92 (brd, J=7.7 Hz, 1 H, Ar), 7.29 (brt, J=8.0 Hz, 1 H, Ar), 7.37 (m, 3 H, 2 Ar and NH), 7.43 (brd, J=7.9 Hz, 1 H, Ar), 7.54 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.64 (d, Jm=1.5 Hz, 1 H, Ar), 8.17 (d, Jo=8.2 Hz, 1 H, Ar), 9.20 (s, 1 H, NH).
