Diisopropylethylamine → (2E)-2-(3-chloro-4-methylsulfonylphenyl)-N-(1-methylpyrazol-3-yl)-2-propan-2-yloxyiminoacetamide

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Reaction Conditions

Reaction Steps

This estimated 80% pure (E)-(3-chloro-4-methanesulfonyl-phenyl)-isopropoxyimino-acetic acid (130 mg, <0.39 mmol) was combined with N,N-diisopropylethylamine (162 μL, 0.93 mmol) and O-(7-azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 mmol) in acetonitrile (1.5 mL) and cooled to 0° C. 1-Methyl-1H-pyrazol-3-ylamine (33 μL, 0.34 mmol) was added and the reaction mixture was allowed to warm to 25° C. and stirred overnight. After evaporating the volatiles under a stream of nitrogen, 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; 60% ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-isopropoxyimino-N-(1-methyl-1H-pyrazol-3-yl)-acetamide (56 mg, 45%) as a slightly yellow solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C16H19ClN4O4S [M+] 398.08, found 399 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.34 (d, J=6.3 Hz, 6 H, 2×CH3), 3.30 (s, 3 H, SO2CH3), 3.86 (s, 3 H, NCH3), 4.57 (m, J=6.3 Hz, 1 H, OCH), 6.70 (d, J=2.3 Hz, 1 H, Ar), 7.29 (d, J=2.3 Hz, 1 H, Ar), 7.58 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.69 (d, Jm=1.5 Hz, 1 H, Ar), 8.19 (d, Jo=8.2 Hz, 1 H, Ar), 9.14 (s, 1 H, NH).

Provenance & Evidence