Ammonium Chloride → 4-(4-Fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carboxamide

HRID 922754Notes

Reaction equation

HRID 922754 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[C:23](=[O:24])[CH2:22][N:21]([CH3:25])[C:20]4=[O:26])=[CH:15][CH:16]=3)[N:11]=[C:10]([C:27]#[N:28])[CH:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=[O:30].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[C:23](=[O:24])[CH2:22][N:21]([CH3:25])[C:20]4=[O:26])=[CH:15][CH:16]=3)[N:11]=[C:10]([C:27]([NH2:28])=[O:30])[CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 159762Sodium percarbonateHCID 715655234-(4-Fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carbonitrile

Product 1

HCID 715665964-(4-Fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carboxamideYield 75%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

4-(4-Fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carbonitrile (2-2, 44.9 mg, 0.120 mmol, 1.0 equiv.) was dissolved in acetone (1.5 mL)/water (0.75 mL) and sodium percarbonate (188.0 mg, 0.600 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 (1.0 mL), extracted with ethyl acetate (3×5.0 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 4-(4-fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carboxamide (2-3, 35.3 mg, 75.0%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.498 (br s, 1H); 8.221 (d, J=1.29 Hz, 1H); 8.180 (s, 1H); 7.947 (d, J=8.60 Hz, 1H); 7.672 (dd, J1=8.79 Hz, JZ=1.83 Hz, 1H); 7.532 (br s, 1H); 7.462-7.512 (m, 2H); 7.219-7.276 (m, 2H); 4.918 (s, 2H); 3.985 (s, 2H); 3.040 (s, 3H). LRMS m/z (M+H)+ 393.1 found, 393.1 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 crude residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)

Sources & evidence

ORD record
ord-152384eeae5c4686ae7bd4a2575e2729
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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