Water → HCID 67499336, compound

HRID 1484725Notes

Reaction equation

HRID 1484725 reaction equation
[CH3:1][N:2]1[C:6]([NH:7][C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])=[CH:5][C:4]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[N:3]1.[H-].[Na+].I[CH2:22][CH3:23].O>CN(C=O)C.C(OCC)(=O)C>[CH2:22]([N:7]([C:6]1[N:2]([CH3:1])[N:3]=[C:4]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:5]=1)[C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])[CH3:23]

Participants

7

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 67499815HCID 67499815, compound

Product 1

HCID 67499336HCID 67499336, compoundYield 30.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(1-methyl-3-(pyridine-3-yl)-1H-pyrazol-5-yl)isobutyramide (0.08 g, 0.33 mmol) in DMF (0.66 ml) at 0° C. was added sodium hydride (0.016 g, 0.39 mmol, 60% dispersion in mineral oil) in one portion and the suspension was stirred for 30 minutes. The ice bath was removed and stirred for an additional 30 minutes. Iodoethane (0.06 g, 0.39 mmol) was added in one portion and stirred overnight at room temperature. Water and ethyl acetate were added and the resulting biphasic mixture was separated. The aqueous layer was extracted one time with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated to dryness. The crude product was purified by silica gel chromatography to give the title compound as a clear oil (27.5 mg, 30%): 1H NMR (300 MHz, CDCl3) δ 9.00 (bs, 1H), 8.57 (s, 1H), 8.09 (dd, J=7.9 Hz, 1H), 7.34 (dd, 1H), 6.48 (s, 1H), 4.00 (m, 1H), 3.76 (s, 3H), 3.36 (m, 1H), 2.33 (m, 1H), 1.17 (t, J=7.1 Hz, 3H), 1.08 (t, J=6.7 Hz, 6H); ESIMS m/z 273 (M+H).

Workup

  1. customThe ice bath was removed
  2. stirringstirred for an additional 30 minutes
  3. stirringstirred overnight at room temperature
  4. customthe resulting biphasic mixture was separated
  5. extractionThe aqueous layer was extracted one time with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-215b895ace854b45a85f3aafe88941d7
Source dataset
uspto-grants-2016_08
Patent number
US09422278B2

Reaction notes

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