Pentanenitrile, 4,4-dimethyl-3-oxo- → 2-[4-(5-Amino-3-tert-butyl-pyrazol-1-yl)-pyridin-2-yloxy]-ethanol

HRID 60667

Reaction equation

HRID 60667 reaction equation
[CH3:1][C:2]([CH3:9])([CH3:8])[C:3](=O)[CH2:4][C:5]#[N:6].O1CCCCC1[O:16][CH2:17][CH2:18][O:19][C:20]1[CH:25]=[C:24]([NH:26][NH2:27])[CH:23]=[CH:22][N:21]=1>CO.Cl>[NH2:6][C:5]1[N:26]([C:24]2[CH:23]=[CH:22][N:21]=[C:20]([O:19][CH2:18][CH2:17][OH:16])[CH:25]=2)[N:27]=[C:3]([C:2]([CH3:9])([CH3:8])[CH3:1])[CH:4]=1

Participants

5

Reactant 2

HCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 117729647{2-[2-(Tetrahydro-pyran-2-yloxy)-ethoxy]-pyridin-4-yl}-hydrazine

Product 1

HCID 1177296752-[4-(5-Amino-3-tert-butyl-pyrazol-1-yl)-pyridin-2-yloxy]-ethanol

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolvent

Procedure

4,4-Dimethyl-3-oxopentanenitrile (293 mg, 2.34 mmol) and Intermediate 67b (593 mg, 2.34 mmol) were suspended in MeOH (10 mL) and a few drops of concentrated HCl added and the reaction heated to reflux for 72 h. The reaction was cooled, concentrated in vacuo and partitioned between H2O and EtOAc. The organic layer was separated, and the aqueous extracted again with EtOAc. The combined organics were dried over MgSO4 and subjected to FCC, eluting with 10-50% EtOAc/cyclohexane to afford the title compound after crystallisation (139 mg, 21%). LCMS (Method 3) Rt 2.77 min, m/z 277.3 [MH+].

Workup

  1. temperaturethe reaction heated
  2. temperatureto reflux for 72 h
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated in vacuo
  5. custompartitioned between H2O and EtOAc
  6. customThe organic layer was separated
  7. extractionthe aqueous extracted again with EtOAc
  8. dry with materialThe combined organics were dried over MgSO4
  9. washeluting with 10-50% EtOAc/cyclohexane

Sources & evidence

ORD record
ord-35d2a798565f44049108b46d4f10a2f8
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Linked notes

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