Reaction Steps
(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 115 mg, 0.33 mmol), 1-pyridin-3-ylmethyl-1H-pyrazol-3-ylamine (72 mg, 0.41 mmol) and N,N-diisopropylethylamine (232 μL, 1.33 mmol) were combined in methylene chloride (1.7 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (139 mg, 0.37 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/chloroform to 5% methanol/chloroform) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-N-(1-pyridin-3-ylmethyl-1H-pyrazol-3-yl)-acetamide (76 mg, 46%) as a white solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C23H24ClN5O4S [M+] 501.12, found 502 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.64 (m, 4 H, 2×CH2), 1.85 (m, 4 H, 2×CH2), 3.28 (s, 3 H, SO2CH3), 4.87 (m, 1 H, OCH), 5.26 (s, 2 H, NCH3), 6.78 (d, J=2.3 Hz, 1 H, Ar), 7.30 (dd, J=7.9, J=4.9 Hz, 1 H, Ar), 7.40 (d, J=2.3 Hz, 1 H, Ar), 7.51 (m, 1 H, Ar), 7.55 (dd, Jo=8.2, Jm=1.6 Hz, 1 H, Ar), 7.65 (d, Jm=1.6 Hz, 1 H, Ar), 8.18 (d, Jo=8.2 Hz, 1 H, Ar), 8.56 (m, 2H, Ar), 9.17 (s, 1 H, NH).
