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

HRID 600983Notes

Reaction equation

HRID 600983 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH2:18][CH:19]([CH3:21])[CH3:20])/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([NH2:28])=[N:24]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH2:18][CH:19]([CH3:21])[CH3:20])/[C:13]([NH:28][C:25]2[CH:26]=[CH:27][N:23]([CH3:22])[N:24]=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 87416786(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-(2-methylpropoxyimino)acetic acid

Product 1

HCID 59745102(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-(2-methylpropoxyimino)-N-(1-methylpyrazol-3-yl)acetamideYield 95.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-isobutoxyimino-acetic acid (104 mg, 0.31 mmol), 1-methyl-1H-pyrazol-3-ylamine (30 mg, 0.31 mmol) and N,N-diisopropylethylamine (163 μL, 0.94 mmol) were combined in methylene chloride (1.5 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (119 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; 50% ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-isobutoxyimino-N-(1-methyl-1H-pyrazol-3-yl)-acetamide (122 mg, 95%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C17H21ClN4O4S [M+] 412.10, found 413 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 0.94 (d, J=6.7 Hz, 6 H, 2×CH3), 2.05 (m, 1 H, CH), 3.29 (s, 3 H, SO2CH3), 3.84 (s, 3 H, NCH3), 4.06 (d, J=6.8 Hz, 2 H, OCH2), 6.68 (d, J=2.3 Hz, 1 H, Ar), 7.28 (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), 9.13 (brs, 1 H, NH).

Workup

  1. temperaturecooled in an ice bath
  2. customthe ice bath was removed
  3. customthe reaction mixture was evaporated in vacuo
  4. additionThe residue was treated with saturated aqueous sodium bicarbonate solution (1 mL)
  5. extractionextracted with chloroform (2×3 mL)
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a43db61f28124104a87f3079cdf24c45
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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