Water → HCID 136146890, compound

HRID 1719093Notes

Reaction equation

HRID 1719093 reaction equation
Cl.[NH2:2]O.[C:4](=[O:7])([O-])[OH:5].[Na+].[F:9][C:10]1([F:50])[CH2:15][CH2:14][CH:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]5[C:38]([C:43]#[N:44])=[CH:39][CH:40]=[CH:41][CH:42]=5)=[CH:33][CH:32]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]=[C:24]3[CH2:48][CH3:49])=[CH:19][CH:18]=2)[CH2:12][CH2:11]1.O>CS(C)=O>[F:50][C:10]1([F:9])[CH2:11][CH2:12][CH:13]([O:16][C:17]2[CH:18]=[CH:19][C:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=5[C:43]5[NH:2][C:4](=[O:7])[O:5][N:44]=5)=[CH:33][CH:32]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]=[C:24]3[CH2:48][CH3:49])=[CH:21][CH:22]=2)[CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 59785859HCID 59785859, compound

Product 1

HCID 136146890HCID 136146890, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of hydroxylamine hydrochloride (661 mg) and sodium hydrogen carbonate (941 mg) in dimethyl sulfoxide (5 mL) was stirred at 40° C. for 30 min, and then 4′-[(1-{4-[(4,4-difluorocyclohexyl)oxy]phenyl}-2-ethyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (635 mg) was added to the mixture, and the mixture was stirred at 90° C. for 12 hr. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (20 mL), and then 1,1′-carbonyldiimidazole (272 mg) and 1,8-diazabicyclo[5,4,0]undec-7-ene (0.25 mL) were added thereto. The mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was successively washed with water and saturated brine (20 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the title compound as a pale yellow amorphous solid (12.1 mg, 2%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 12 hr
  2. filtrationthe precipitated solid was collected by filtration
  3. dissolutionThe obtained solid was dissolved in ethyl acetate
  4. washThe solution was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated
  7. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
  8. addition1,1′-carbonyldiimidazole (272 mg) and 1,8-diazabicyclo[5,4,0]undec-7-ene (0.25 mL) were added
  9. stirringThe mixture was stirred at room temperature for 2 hr
  10. additionThe reaction mixture was diluted with ethyl acetate
  11. washthe mixture was successively washed with water and saturated brine (20 mL)
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-25f87a173d28457b9f2b01e2f1861c8f
Source dataset
uspto-grants-2010_09
Patent number
US07803940B2

Reaction notes

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