Ammonium Chloride → 4-(4-Fluorophenyl)-7-((4-formyl-1H-pyrazol-1-yl)methyl)quinoline-2-carboxamide

HRID 922764Notes

Reaction equation

HRID 922764 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH2:18][N:19]4[CH:23]=[C:22]([CH:24]=[O:25])[CH:21]=[N:20]4)=[CH:15][CH:16]=3)[N:11]=[C:10]([C:26]#[N:27])[CH:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=[O:29].C([O-])([O-])=O.OO.OO.OO.[Na+].[Na+].[Na+].[Na+].[NH4+].[Cl-]>CC(C)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH2:18][N:19]4[CH:23]=[C:22]([CH:24]=[O:25])[CH:21]=[N:20]4)=[CH:15][CH:16]=3)[N:11]=[C:10]([C:26]([NH2:27])=[O:29])[CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 159762Sodium percarbonateHCID 895437484-(4-Fluorophenyl)-7-[(4-formyl-1H-pyrazol-1-yl)methyl]-2-quinolinecarbonitrile

Product 1

HCID 895451674-(4-Fluorophenyl)-7-((4-formyl-1H-pyrazol-1-yl)methyl)quinoline-2-carboxamideYield 74.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

4-(4-Fluorophenyl)-7-[(4-formyl-1H-pyrazol-1-yl)methyl]quinoline-2-carbonitrile (3-8), 51 mg, 0.143 mmol, 1.0 equiv.) was dissolved in acetone (1.0 mL)/water (0.5 mL) and sodium percarbonate (225.0 mg, 0.716 mmol, 5.0 equiv) was added. The resulting mixture was stirred at 50° C. for two hours. The mixture was cooled and poured over aqueous NH4Cl (saturate, 1.0 mL), extracted with Ethyl Acetate (3×5.0 mL), dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 4-(4-Fluorophenyl)-7-[(4-formyl-1H-pyrazol-1-yl)methyl]quinoline-2-carbonitrile (3-9, 40.0 mg, 74.7%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 9.879 (s, 1H); 8.262 (s, 1H); 8.056 (br s, 2H); 8.021 (br s, 2H); 7.972 (d, J=8.80 Hz, 1H); 7.462-7.512 (m, 3H); 7.216-7.259 (m, 2H); 5.705 (br s, 1H); 5.589 (s, 2H). LRMS m/z (M+H)+ 375.1 found, 375.1 required.

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled
  3. extractionextracted with Ethyl Acetate (3×5.0 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)

Sources & evidence

ORD record
ord-597eb88405274092ae8bb01bde62857c
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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