Hydroxyamine hydrochloride → 2-butyl-5-(4-isopropoxyphenyl)-6-methyl-3-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one

HRID 1674398Notes

Reaction equation

HRID 1674398 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[C:31]([C:36]#[N:37])=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:26][CH:25]=2)[C:7](=[O:22])[C:8]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:14][CH:13]=2)=[C:9]([CH3:11])[N:10]=1)[CH2:2][CH2:3][CH3:4].Cl.[NH2:39]O.[C:41](=[O:44])([O-])[OH:42].[Na+]>CS(C)=O.C(OCC)(=O)C>[CH2:1]([C:5]1[N:6]([CH2:23][C:24]2[CH:25]=[CH:26][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]3[NH:39][C:41](=[O:44])[O:42][N:37]=3)=[CH:28][CH:29]=2)[C:7](=[O:22])[C:8]([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH:19]([CH3:20])[CH3:21])=[CH:16][CH:17]=2)=[C:9]([CH3:11])[N:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 574604204'-{[2-butyl-5-(4-isopropoxyphenyl)-4-methyl-6-oxopyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1360269702-butyl-5-(4-isopropoxyphenyl)-6-methyl-3-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-oneYield 78.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

4′-{[2-Butyl-5-(4-isopropoxyphenyl)-4-methyl-6-oxopyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (0.56 g) was dissolved in dimethyl sulfoxide (5 mL), and hydroxylamine hydrochloride (0.79 g) and sodium hydrogen carbonate (1.2 g) were added. The mixture was stirred overnight at 90° C. After cooling, the reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), and N,N′-carbonyldiimidazole (0.28 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.26 mL) were added. After stirring for 30 min, the reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.49 g, 78%).

Workup

  1. temperatureAfter cooling
  2. washwashed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  6. additionN,N′-carbonyldiimidazole (0.28 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.26 mL) were added
  7. stirringAfter stirring for 30 min
  8. additionthe reaction mixture was diluted with ethyl acetate
  9. washwashed with 1 M hydrochloric acid
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5d72d46c6b2d44548d147dfda6ee643b
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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