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

HRID 1674404Notes

Reaction equation

HRID 1674404 reaction equation
[CH3:1][C:2]1([CH3:38])[CH2:6][C:5]2[CH:7]=[C:8]([C:11]3[C:16](=[O:17])[N:15]([CH2:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]5[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=5)=[CH:21][CH:20]=4)[C:14]([CH2:33][CH2:34][CH3:35])=[N:13][C:12]=3[CH2:36][CH3:37])[CH:9]=[CH:10][C:4]=2[O:3]1.Cl.[NH2:40]O.[C:42](=[O:45])([O-])[OH:43].[Na+]>CS(C)=O.C(OCC)(=O)C>[CH3:38][C:2]1([CH3:1])[CH2:6][C:5]2[CH:7]=[C:8]([C:11]3[C:16](=[O:17])[N:15]([CH2:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[C:31]5[NH:40][C:42](=[O:45])[O:43][N:32]=5)=[CH:21][CH:20]=4)[C:14]([CH2:33][CH2:34][CH3:35])=[N:13][C:12]=3[CH2:36][CH3:37])[CH:9]=[CH:10][C:4]=2[O:3]1

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 594693844'-{[5-(2,2-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-4-ethyl-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1361466735-(2,2-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-6-ethyl-3-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-2-propylpyrimidin-4(3H)-oneYield 74.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

4′-{[5-(2,2-Dimethyl-2,3-dihydro-1-benzofuran-5-yl)-4-ethyl-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (0.58 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 (0.48 g, 74%).

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-0865dc69ee33410f979da5066683dd49
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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