Water → HCID 135845010, compound

HRID 1673753Notes

Reaction equation

HRID 1673753 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].[CH:9]([O:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:24](=[O:25])[C:23]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[C:34]([C:39]#[N:40])=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:29][CH:28]=3)=[C:22]([CH2:41][CH2:42][CH3:43])[N:21]=[C:20]2[CH3:44])=[CH:15][CH:14]=1)([CH3:11])[CH3:10].O>CS(C)=O>[CH:9]([O:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[C:24](=[O:25])[C:23]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[C:39]4[NH:3][C:4](=[O:7])[O:5][N:40]=4)=[CH:29][CH:28]=3)=[C:22]([CH2:41][CH2:42][CH3:43])[N:21]=[C:20]2[CH3:44])=[CH:17][CH:18]=1)([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 962WaterHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 574602664'-{[1-(4-Isopropoxyphenyl)-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 135845010HCID 135845010, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a suspension of hydroxylammonium chloride (186 g) in dimethyl sulfoxide (1340 mL) was added sodium hydrogen carbonate (280 g) at 50° C. and stirred for 30 min, and then 4′-{[1-(4-isopropoxyphenyl)-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (160 g) was added to the mixture. After being stirred at 90° C. for 18 hr, the mixture was allowed to cool to room temperature and the mixture was poured into iced water. The mixture was stirred for 30 min and the precipitate was collected. The solid was washed with water and dried in vacuo at 80° C. The solid was dissolved in tetrahydrofuran (1300 mL), N,N′-carbonyldiimidazole (65 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (60 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid 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 (152 g, 85%).

Workup

  1. stirringAfter being stirred at 90° C. for 18 hr
  2. stirringThe mixture was stirred for 30 min
  3. customthe precipitate was collected
  4. washThe solid was washed with water
  5. customdried in vacuo at 80° C
  6. dissolutionThe solid was dissolved in tetrahydrofuran (1300 mL)
  7. additionN,N′-carbonyldiimidazole (65 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (60 mL) were added
  8. stirringthe mixture was stirred at room temperature for 2 hr
  9. additionThe reaction mixture was diluted with ethyl acetate
  10. washwashed with 1 M hydrochloric acid
  11. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6b180f2e724140e295eb3f737876a18b
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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