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

HRID 1674396Notes

Reaction equation

HRID 1674396 reaction equation
[CH2:1]([C:3]1[N:4]=[C:5]([CH2:35][CH2:36][CH3:37])[N:6]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[C:28]([C:33]#[N:34])=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:23][CH:22]=2)[C:7](=[O:19])[C:8]=1[C:9]1[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[CH:11][CH:10]=1)[CH3:2].Cl.[NH2:39]O.[C:41](=[O:44])([O-])[OH:42].[Na+]>CS(C)=O.C(OCC)(=O)C>[CH2:1]([C:3]1[N:4]=[C:5]([CH2:35][CH2:36][CH3:37])[N:6]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]3[NH:39][C:41](=[O:44])[O:42][N:34]=3)=[CH:25][CH:26]=2)[C:7](=[O:19])[C:8]=1[C:9]1[CH:10]=[CH:11][C:12]([O:15][CH:16]([CH3:17])[CH3:18])=[CH:13][CH:14]=1)[CH3:2]

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 574604194'-{[4-ethyl-5-(4-isopropoxyphenyl)-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1360269696-ethyl-5-(4-isopropoxyphenyl)-3-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-2-propylpyrimidin-4(3H)-oneYield 79%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

4′-{[4-Ethyl-5-(4-isopropoxyphenyl)-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (0.5 g) was dissolved in dimethyl sulfoxide (5 mL), and hydroxylamine hydrochloride (0.71 g) and sodium hydrogen carbonate (1 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 (0.25 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 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 (0.44 g, 79%).

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 (0.25 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 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-1e44068cb3304d3d8673a5a815fd7fcf
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

Loading…