2-Methylbenzonitrile → [4-(5-Ethyl-3-pyridin-3-yl-pyrazol-1-yl)phenyl]-(2-methylbenzyl)amine

HRID 1634107Notes

Reaction equation

HRID 1634107 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[N:6]=[C:5]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:4]=1)[CH3:2].[C:21]1([CH3:29])[C:22]([C:27]#N)=[CH:23][CH:24]=[CH:25][CH:26]=1>C(O)(=O)C.[Ni]>[CH2:1]([C:3]1[N:7]([C:8]2[CH:9]=[CH:10][C:11]([NH:14][CH2:29][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[CH3:27])=[CH:12][CH:13]=2)[N:6]=[C:5]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:4]=1)[CH3:2]

Participants

5

Reactant 2

HCID 107212-MethylbenzonitrileHCID 186770941-(4-Aminophenyl)-3-(3-pyridyl)-5-ethylpyrazole

Product 1

HCID 9842224[4-(5-Ethyl-3-pyridin-3-yl-pyrazol-1-yl)phenyl]-(2-methylbenzyl)amineYield 85%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 176Acetic AcidSolvent

Procedure

A slurry of Raney Ni (200 mg, 50% in water) was added to a solution 5-ethyl-3-(3-pyridyl)-1-(4′-aminophenyl)pyrazole (500 mg, 1.89 mmol) and o-tolunitrile (0.27 mL, 1.2 equiv.) in glacial acetic acid (20 mL), and the mixture was stirred under hydrogen at 40 psi for 7.5 h. The reaction mixture was filtered through diatomaceous earth, diluted with water, extracted with ethyl acetate, washed with brine, dried (Na2SO4) and concentrated. Chromatography on silica gel (hexane/ethyl acetate=1:1) gave the title compound (595 mg, 85%). 1H-NMR (CDCl3): 1.30 (t, J=7.5 Hz, 3H), 2.42 (s, 3H), 2.69 (q, J=7.5 Hz, 2H), 3.95-4.25 (bs, 1H), 4.36 (s, 2H), 6.58 (s, 1H), 6.72 (d, J=8.7 Hz, 1H), 7.21-7.41 (m, 6H), 8.21 (dd, J=1.6, 6.3 Hz, 1H), 8.56 (d, J=4.1 Hz, 1H), 9.10 (d, J=1.6 Hz, 1H).

Workup

  1. filtrationThe reaction mixture was filtered through diatomaceous earth
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-65ee236e77d24c0584e535b733a23dd9
Source dataset
uspto-grants-2003_01
Patent number
US06506747B1

Reaction notes

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