Sodium Hydroxide → 3-[5-amino-4-(4-methyl-benzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methyl-benzamide

HRID 2041037Notes

Reaction equation

HRID 2041037 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[CH3:14])[C:5]([NH:7][CH:8]1[CH2:10][CH2:9]1)=[O:6].[C:15]1([CH3:25])[CH:20]=[CH:19]C(S(O)(=O)=O)=[CH:17][CH:16]=1.N[CH:27]([C:30]#[N:31])[C:28]#[N:29].[C:32]([O-:35])(=O)[CH3:33].[Na+].[OH-].[Na+]>C(OCC)(OCC)OCC.O>[NH2:31][C:30]1[N:1]([C:2]2[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=2[CH3:14])[C:5]([NH:7][CH:8]2[CH2:9][CH2:10]2)=[O:6])[N:29]=[CH:28][C:27]=1[C:32](=[O:35])[C:33]1[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 517045Sodium AcetateHCID 563049Aminomalononitrile p-toluenesulphonateHCID 119838543-amino-N-cyclopropyl-4-methylbenzamide

Product 1

HCID 111647033-[5-amino-4-(4-methyl-benzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methyl-benzamideYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31214Ethyl orthoformateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-amino-N-cyclopropyl-4-methyl-benzamide 1 (380 mg, 2.0 mmol) in 2.0 mL of triethyl orthoformate was stirred at 120° C. in microwave for 20 minutes. The solvent was removed under reduced pressure. The residue was dissolved in 5 mL of acetic acid and then was added aminomalononitrile p-toluenesulfonate (506 mg, 2.0 mmol) and sodium acetate (164 mg, 2.0 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was diluted with 20 mL of water and then its pH was adjusted to 8.0 by aqueous NaOH. The resulting mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated in vacuo evaporated. The residue was purified by silica gel column chromatography (10/1, methylene chloride:methanol) to give 3-(5-amino-4-cyano-imidazol-1-yl)-N-cyclopropyl-4-methyl-benzamide 3 as a colorless solid (170 mg, 30%). HPLC (4 minute gradient) tR=1.39 min; MS m/z 282 [M+H].

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in 5 mL of acetic acid
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. extractionThe resulting mixture was extracted with EtOAc (3×50 mL)
  5. washThe combined organic layers were washed with water (10 mL) and brine (10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customevaporated
  10. customThe residue was purified by silica gel column chromatography (10/1, methylene chloride:methanol)

Sources & evidence

ORD record
ord-8bbd313feac24ac891fb457ceac6a451
Source dataset
uspto-grants-2013_11
Patent number
US08580838B2

Reaction notes

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