Pyrazole → HCID 14450247, compound

HRID 406837Notes

Reaction equation

HRID 406837 reaction equation
F[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH3:8])[CH:7]=1.[NH:12]1[CH:16]=[CH:15][CH:14]=[N:13]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[CH3:8][C:6]1[CH:7]=[C:2]([N:12]2[CH:16]=[CH:15][CH:14]=[N:13]2)[CH:3]=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10]

Participants

6

Reactant 3

HCID 1048PyrazoleHCID 11430Potassium CarbonateHCID 949565-Fluoro-2-nitrotoluene

Product 1

HCID 14450247HCID 14450247, compoundYield 106.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-fluoro-2-nitrotoluene (1.27 g, 8.20 mmol) and pyrazole (1.3 g, 19.3 mmol) in dimethylformamide (32 mL) was added potassium carbonate (1.3 g, 9.7 mmol), and the mixture was heated to 100° C. overnight. The reaction was cooled, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with 10% aqueous lithium chloride, water and saturated sodium chloride, then dried over sodium sulfate and concentrated on a rotary evaporator to give 1-(3-methyl-4-nitrophenyl)-1H-pyrazole (1.78 g, 100%). This material was dissolved in ethanol (50 mL) and, after addition of 5% palladium on carbon (100 mg), the reaction was stirred under a balloon of hydrogen overnight. The mixture was filtered through Celite and washed with ethanol. The solvent was removed on a rotary evaporator to give 2-methyl-4-(1H-pyrazol-1-yl)aniline. A portion of this material (52 mg, 0.30 mmol) was added to a solution of 4-(4-phenylquinazolin-2-ylamino)benzoyl chloride (110 mg, 0.30 mmol) and Hunig's base (157 μL, 0.90 mmol) in tetrahydrofuran (2 mL) and the reaction was allowed to stir at rt overnight. The mixture was concentrated on a rotary evaporator and purified by flash column chromatography to give N-[2-methyl-4-(1H-pyrazol-1-yl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide (90 mg, 60%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.30 (s, 1H), 9.80 (s, 1H), 8.50 (d, 1H), 8.20 (d, 2H), 8.02 (d, 2H), 7.86 (m, 3H), 7.80 (m, 3H), 7.75 (d, 1H), 7.70 (dd, 1H), 7.64 (t, 3H), 7.50 (d, 1H), 7.42 (m, 1H), 6.58 (t, 1H), 2.30 (s, 3H). MS (EI) for C31H24N6O: 497.4 (MH+).

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with ethyl acetate
  3. washThe combined organic extracts were washed with 10% aqueous lithium chloride, water and saturated sodium chloride
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-b168d93cc42c40e2b8e3c6b209ae529c
Source dataset
uspto-grants-2014_06
Patent number
US08754092B2

Reaction notes

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