Hydroxylamine HCl → 7-butyl-6-{[3,5-difluoro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one
Reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].[CH2:9]([C:13]1[N:18]2[N:19]=[CH:20][N:21]=[C:17]2[N:16](COC)[C:15](=[O:25])[C:14]=1[CH2:26][C:27]1[C:32]([F:33])=[CH:31][C:30]([C:34]2[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=2)=[CH:29][C:28]=1[F:42])[CH2:10][CH2:11][CH3:12].B(Br)(Br)Br>C(OCC)(=O)C.C(Cl)Cl.O.CS(C)=O>[CH2:9]([C:13]1[N:18]2[N:19]=[CH:20][N:21]=[C:17]2[NH:16][C:15](=[O:25])[C:14]=1[CH2:26][C:27]1[C:32]([F:33])=[CH:31][C:30]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[C:40]2[NH:3][C:4](=[O:7])[O:5][N:41]=2)=[CH:29][C:28]=1[F:42])[CH2:10][CH2:11][CH3:12]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 40 °C
Procedure
A mixture of hydroxylammonium chloride (0.87 g), sodium hydrogen carbonate (1.4 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[7-butyl-4-(methoxymethyl)-5-oxo-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3′,5′-difluorobiphenyl-2-carbonitrile (0.39 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.16 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.14 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 hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by purification by silica gel column chromatography was dissolved in methylene chloride solution (10 mL), boron tribromide (1.0 M methylene chloride solution, 2.2 mL) was added, and the mixture was stirred at room temperature for 1 day. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.029 g, 7%).
Workup
- stirringthe mixture was stirred at 90° C. for 16 hr
- washwashed with water
- dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
- customThe solvent was evaporated under reduced pressure
- dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
- additionN,N′-Carbonyldiimidazole (0.16 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.14 mL) were added
- stirringthe mixture was stirred at room temperature for 2 hr
- additionThe reaction mixture was diluted with ethyl acetate
- washwashed with saturated aqueous potassium hydrogensulfate solution
- dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
- customThe solvent was evaporated under reduced pressure
- customThe residue obtained by purification by silica gel column chromatography
- stirringthe mixture was stirred at room temperature for 1 day
- extractionthe mixture was extracted with ethyl acetate
- washThe organic layer was washed with saturated brine
- dry with materialdried over anhydrous magnesium sulfate
- customthe solvent was evaporated
- customThe residue was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-80adc196451b409e802afa5f81ac29bf
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08283353B2
Reaction notes
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