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

HRID 600954Notes

Reaction equation

HRID 600954 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]([CH3:20])[CH3:19])/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(N(CC)C(C)C)(C)C.[CH3:30][N:31]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32]1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]([CH3:20])[CH3:19])/[C:13]([NH:36][C:33]2[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1372541-Methyl-3-aminopyrazoleHCID 87416770(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-propan-2-yloxyiminoacetic acid

Product 1

HCID 59745094(2E)-2-(3-chloro-4-methylsulfonylphenyl)-N-(1-methylpyrazol-3-yl)-2-propan-2-yloxyiminoacetamideYield 45%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  1. temperatureto warm to 25° C.
  2. customAfter evaporating the volatiles under a stream of nitrogen
  3. additionThe residue was treated with saturated aqueous sodium bicarbonate solution (1 mL)
  4. extractionextracted with chloroform (2×3 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-cde36de2307847268a6b43dc8a751e34
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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