Hydroxylamine HCl → HCID 136026836, compound

HRID 1673714Notes

Reaction equation

HRID 1673714 reaction equation
[CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].Br[CH2:31][C:32]1[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:39].[Cl-].O[NH3+:42].[C:43](=[O:46])([O-])[OH:44].[Na+]>C(OCC)(=O)C.CS(C)=O.CN(C)C=O>[CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[N:8]([CH2:31][C:32]2[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:39])[C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]2[NH:42][C:43](=[O:46])[O:44][N:25]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4]

Participants

9

Reactant 5

HCID 21645Hydroxylamine HClHCID 24758Sodium hydrideHCID 301591-Bromomethyl-2,6-dichlorobenzeneHCID 516892Sodium BicarbonateHCID 1354012224'-[(4-Butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile

Product 1

HCID 136026836HCID 136026836, compoundYield 3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1 g), sodium hydride (0.13 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 10 min, 2-(bromomethyl)-1,3-dichlorobenzene (0.81 mL) was added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by silica gel column chromatography was dissolved in dimethyl sulfoxide (5 mL), and added to a mixture of hydroxylammonium chloride (0.4 g), sodium hydrogen carbonate (0.65 g) and dimethyl sulfoxide (10 mL) previously stirred at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr, and diluted with ethyl acetate. The mixture was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL), N,N′-carbonyldiimidazole (0.075 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.064 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.047 g, 3%).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hr
  2. washwashed with 5% aqueous potassium hydrogen sulfate solution
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue obtained by silica gel column chromatography
  6. stirringpreviously stirred at 40° C. for 30 min
  7. stirringThe reaction mixture was stirred at 90° C. for 16 hr
  8. washThe mixture was washed with water
  9. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
  12. additionN,N′-carbonyldiimidazole (0.075 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.064 mL) were added
  13. stirringthe mixture was stirred at room temperature for 2 hr
  14. additionThe reaction mixture was diluted with ethyl acetate
  15. washwashed with saturated aqueous potassium hydrogen sulfate solution
  16. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  17. customThe solvent was evaporated under reduced pressure
  18. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7efc5eb113204d05bc4bda82b0796236
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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