Diisopropylethylamine → (2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyimino-N-(1-methylpyrazol-3-yl)acetamide

HRID 600962Notes

Reaction equation

HRID 600962 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)/[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.[CH3:33][N:34]1[CH:38]=[CH:37][C:36]([NH2:39])=[N:35]1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]2)/[C:13]([NH:39][C:36]2[CH:37]=[CH:38][N:34]([CH3:33])[N:35]=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 87416752(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetic acid

Product 1

HCID 59745098(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyimino-N-(1-methylpyrazol-3-yl)acetamideYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclohexyloxyimino-acetic acid (112 mg, 0.31 mmol), N,N-diisopropylethylamine (163 μL, 0.94 mmol) and 1-methyl-1H-pyrazol-3-ylamine (30 μL, 0.31 mmol) were combined in methylene chloride (1.5 mL) and cooled to 0° C. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 mmol) was added and the cooling bath was removed. After stirring 16 h, the reaction mixture was diluted with chloroform (2 mL) and washed with saturated aqueous sodium bicarbonate solution (1.5 mL). The aqueous phase was extracted with chloroform (1.5 mL) and the combined organic phases were filtered through sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclohexyloxyimino-N-(1-methyl-1H-pyrazol-3-yl)-acetamide (110 mg, 81%) as a white solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C19H23ClN4O4S [M+] 438.11, found 439 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.24-1.61 (m, 6H, 3×CH2), 1.71 (m, 2H, 2×CH of CH2), 1.96 (m, 2H, 2×CH of CH2), 3.29 (s, 3 H, SO2CH3), 3.85 (s, 3 H, NCH3), 4.29 (m, 1 H, OCH), 6.69 (d, J=2.3 Hz, 1 H, Ar), 7.28 (d, J=2.3 Hz, 1 H, Ar), 7.60 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.71 (d, Jm=1.5 Hz, 1 H, Ar), 8.20 (d, Jo=8.2 Hz, 1 H, Ar), 9.15 (s, 1 H, NH).

Workup

  1. customthe cooling bath was removed
  2. additionthe reaction mixture was diluted with chloroform (2 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (1.5 mL)
  4. extractionThe aqueous phase was extracted with chloroform (1.5 mL)
  5. filtrationthe combined organic phases were filtered through sodium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-44a559c5f25f4de786531925e40fa0c7
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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