Acetic Acid → 2-{[3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzamide

HRID 915595Notes

Reaction equation

HRID 915595 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([NH2:7])[N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH3:14])[N:3]=1.Br[C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>CN(C=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:16]2[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=2[C:18]([NH2:20])=[O:19])[N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH3:14])[N:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 776162-BromobenzamideHCID 7756883-Methyl-1-(2-methylphenyl)-1H-pyrazol-5-amine2×

Product 1

HCID 100408062-{[3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzamideYield 21.6%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-amine (Intermediate F, 1.00 g, 5.3 mmol), 2-bromobenzamide (1.07 g, 5.3 mmol), potassium carbonate (0.89 g, 6.4 mmol), and copper (II) acetate (39 mg, 0.2 mmol) in DMF (20 mL) was heated (150° C.) in a sealed tube for 18 h. After cooling, the solution was adjusted to pH=4 using glacial acetic acid. The reaction mixture was extracted with dichloromethane (3×20 mL), and then the combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 33-50% ethyl acetate/hexane afforded a yellow solid that was washed with diethyl ether to give 2-{[3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzamide (350 mg, 21%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 10.48 (s, 1H), 8.01 (s, 1H), 7.67 (dd, 1H), 7.32 (m, 7H), 6.77 (ddd, 1H), 6.08 (s, 1H), 2.19 (s, 3H), 2.00 (s, 3H); ES-MS m/z 307.1 (MH+); HPLC RT (min) 2.41.

Workup

  1. temperatureAfter cooling
  2. extractionThe reaction mixture was extracted with dichloromethane (3×20 mL)
  3. washthe combined organic extracts were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customFlash chromatography of the residue over silica gel using 33-50% ethyl acetate/hexane afforded a yellow solid
  8. washthat was washed with diethyl ether

Sources & evidence

ORD record
ord-c35eb3343acc4f668b2a134797d2e5b3
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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