Ethanol → HCID 136336871, compound

HRID 1057204Notes

Reaction equation

HRID 1057204 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[C:9](/[CH2:36][CH3:37])=[C:10](\[C:26]1[CH:31]=[CH:30][C:29](/[CH:32]=[CH:33]/[C:34]#[N:35])=[CH:28][CH:27]=1)/[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16](C1CCCCO1)[N:15]=[CH:14]2.[NH2:38][OH:39].[CH2:40]([OH:42])C>>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[C:9](/[CH2:36][CH3:37])=[C:10](\[C:26]1[CH:27]=[CH:28][C:29](/[CH:32]=[CH:33]/[C:34]2[NH:35][C:40](=[O:42])[O:39][N:38]=2)=[CH:30][CH:31]=1)/[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][N:15]=[CH:14]2

Participants

4

Reactant 3

HCID 702EthanolHCID 787HydroxylamineHCID 66802474HCID 66802474, compound

Product 1

HCID 136336871HCID 136336871, compound

Procedure

A mixture of (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylonitrile (920 mg, 1.8 mmol) and hydroxylamine (0.18 mL, 2.7 mmol, 50% wt. in water) in ethanol (2 mL) was heated at reflux for 16 h. The ethanol was removed in vacuo, and dichloromethane and water were added. The aqueous layer was extracted with dichloromethane (2×), and the combined organics were washed with brine, dried (MgSO4) and concentrated. Purification by silica gel chromatography (0 to 70% EtOAc/hexanes) provided 433 mg of the title compound as a pale yellow foam. LCMS: 461 [(M-THP+H)+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  3. customThe ethanol was removed in vacuo, and dichloromethane and water
  4. additionwere added
  5. extractionThe aqueous layer was extracted with dichloromethane (2×)
  6. washthe combined organics were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (0 to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-155bee68a30e478f9f92e795adae3152
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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