1-Propanol → HCID 66958580, compound

HRID 2283772Notes

Reaction equation

HRID 2283772 reaction equation
[CH2:1]([N:8]1[C:12]([CH3:13])=[C:11](Br)[C:10]([C:15]#[N:16])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][C:18]([CH3:32])([CH3:31])[C:19]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O)=[O:20].C(O)CC.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC)(C)(C)C.O>[CH2:1]([N:8]1[C:12]([CH3:13])=[C:11]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[NH:21][C:19](=[O:20])[C:18]([CH3:31])([CH3:17])[CH3:32])[C:10]([C:15]#[N:16])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 41935022-(tert-Butylcarbonylamino)phenylboronic acidHCID 669586391-Benzyl-4-bromo-5-methyl-1H-pyrazole-3-carbonitrile

Product 1

HCID 66958580HCID 66958580, compoundYield 59.1%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

1-Benzyl-4-bromo-5-methyl-1H-pyrazole-3-carbonitrile (3.00 g, 10.9 mmol) was treated with triphenylphosphine (85 mg, 0.32 mmol), 2-[(2,2-dimethylpropanoyl)amino]phenylboronic acid (prepared as described in Part G of Example 23, 2.15 g, 16.3 mmol), 1-propanol (22 mL), palladium (II) acetate (24 mg, 0.11 mmol), aqueous sodium carbonate (6.5 mL of 2 M, 13 mmol), and water (4.4 mL) according to the general procedure described in Example 34. The reaction time was approximately 16 hours and no additional reagents were added. The reaction was allowed to cool to ambient temperature and methyl tert-butyl ether (25 mL) was added. After the mixture was stirred for about 10 minutes, the layers were separated. The organic layer was dried over magnesium sulfate, filtered, and concentrated to yield a brown oil. The crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution 1-30% ethyl acetate in hexanes). The appropriate fractions were combined, dried over magnesium sulfate, filtered, and concentrated to yield 2.40 g of N-[2-(1-benzyl-3-cyano-5-methyl-1H-pyrazol-4-yl)phenyl]-2,2-dimethylpropanamide as an oil that solidified upon standing at ambient temperature.

Workup

  1. additionno additional reagents were added
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield a brown oil
  7. customThe crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution 1-30% ethyl acetate in hexanes)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-63e9d0e84f8d4b19851fc2f1bbb86499
Source dataset
uspto-grants-2015_09
Patent number
US09145410B2

Reaction notes

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