Water → HCID 66958637, compound

HRID 1984432Notes

Reaction equation

HRID 1984432 reaction equation
Br[C:2]1[C:3]([C:11]#[N:12])=[N:4][N:5]([CH2:9][CH3:10])[C:6]=1[CH2:7][CH3:8].[CH3:13][C:14]([CH3:30])([CH3:29])[C:15]([NH:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=1B(O)O)=[O:16].C(=O)([O-])[O-].[Na+].[Na+].O>C(O)CC.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:11]([C:3]1[C:2]([C:19]2[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:18]=2[NH:17][C:15](=[O:16])[C:14]([CH3:29])([CH3:13])[CH3:30])=[C:6]([CH2:7][CH3:8])[N:5]([CH2:9][CH3:10])[N:4]=1)#[N:12]

Participants

8

Reactant 4

HCID 962Water2×HCID 10340Sodium CarbonateHCID 15197825HCID 15197825, compoundHCID 66958276HCID 66958276, compound

Product 1

HCID 66958637HCID 66958637, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

A 50 mL round bottom flask containing a mixture of 4-bromo-1,5-diethyl-1H-pyrazole-3-carbonitrile (prepared as described in Part E of Example 11, 1.12 g, 4.91 mmol) and 2-[(2,2-dimethylpropanoyl)amino]-4-methoxyphenylboronic acid (1.36 g, 5.40 mmol) in 1-propanol (25 mL) was evacuated and backfilled with nitrogen. To the flask was added triphenylphosphine (38.6 mg, 0.147 mmol), 2 M aqueous sodium carbonate (7.4 mL), water (5 mL), and palladium (II) acetate (11 mg, 0.048 mmol). The yellow suspension was heated at 100° C. After 3 hours, the reaction mixture was allowed to cool to room temperature, water (10 mL) was added, and the 1-propanol was removed under reduced pressure. The water layer was extracted with ethyl acetate (2×30 mL). The organic layers were combined, washed with 2 M aqueous sodium carbonate (50 mL), water (50 mL), and brine (50 mL), then dried over sodium sulfate. The organic layer was concentrated under reduced pressure. The crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-40% ethyl acetate in hexanes) to provide 0.54 g of N-[2-(3-cyano-1,5-diethyl-1H-pyrazol-4-yl)-5-methoxyphenyl]-2,2-dimethylpropanamide as a colorless liquid.

Workup

  1. additionA 50 mL round bottom flask containing
  2. customwas evacuated
  3. temperatureto cool to room temperature
  4. customthe 1-propanol was removed under reduced pressure
  5. extractionThe water layer was extracted with ethyl acetate (2×30 mL)
  6. washwashed with 2 M aqueous sodium carbonate (50 mL), water (50 mL), and brine (50 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationThe organic layer was concentrated under reduced pressure
  9. customThe crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-323dc9305de94ab98017a854fa9361d1
Source dataset
uspto-grants-2009_06
Patent number
US07544697B2

Reaction notes

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