Diisopropylethylamine → (2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyimino-N-(3-methyl-1,2,4-thiadiazol-5-yl)acetamide

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Reaction Steps

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclohexyloxyimino-acetic acid (prepared as in Example 9, 112 mg, 0.31 mmol), 3-methyl-[1,2,4]thiadiazol-5-ylamine (36 mg, 0.31 mmol) and N,N-diisopropylethylamine (163 μL, 0.93 mmol) were combined in acetonitrile (1.25 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 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; 40% ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclohexyloxyimino-N-(3-methyl-[1,2,4]thiadiazol-5-yl)-acetamide (57 mg, 40%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C18H21ClN4O4S2 [M+] 456.07, found 457 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.25-1.64 (m, 6H, 3×CH2), 1.73 (m, 2H, 2×CH of CH2), 2.00 (m, 2H, 2×CH of CH2), 2.60 (s, 3 H, ArCH3), 3.31 (s, 3 H, SO2CH3), 4.37 (m, 1 H, OCH), 7.64 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.74 (d, Jm=1.5 Hz, 1 H, Ar), 8.23 (d, Jo=8.2 Hz, 1 H, Ar), 10.35 (s, 1 H, NH).

Provenance & Evidence