Hydroxylamine HCl → 4-(1-ethylpiperidin-4-yl)-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

HRID 2063081Notes

Reaction equation

HRID 2063081 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].[CH2:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[C:22](=[O:23])[C:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([C:31]4[C:32]([C:37]#[N:38])=[CH:33][CH:34]=[CH:35][CH:36]=4)=[CH:27][CH:26]=3)=[C:20]([CH2:39][CH2:40][CH3:41])[N:19]3[N:42]=[CH:43][N:44]=[C:18]23)[CH2:13][CH2:12]1)[CH3:10]>CS(C)=O.C(OCC)(=O)C>[CH2:9]([N:11]1[CH2:12][CH2:13][CH:14]([N:17]2[C:22](=[O:23])[C:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[C:37]4[NH:3][C:4](=[O:7])[O:5][N:38]=4)=[CH:27][CH:26]=3)=[C:20]([CH2:39][CH2:40][CH3:41])[N:19]3[N:42]=[CH:43][N:44]=[C:18]23)[CH2:15][CH2:16]1)[CH3:10]

Participants

6

Reactant 3

HCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 670095854'-{[4-(1-Ethylpiperidin-4-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1360637784-(1-ethylpiperidin-4-yl)-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-oneYield 35%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of hydroxylammonium chloride (313 mg), sodium hydrogen carbonate (504 mg) and dimethyl sulfoxide (3 mL) was stirred at 60° C. for 30 min, a solution of 4′-{[4-(1-ethylpiperidin-4-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (145 mg) in dimethyl sulfoxide (2 mL) was added, and the mixture was stirred at 90° C. for 17 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 (58 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (55 mg) were added, and the mixture was stirred at room temperature for 15 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, and the residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=10/90→30/70 (volume ratio)] and crystallized from acetonitrile to give the title compound as colorless crystals (57 mg, 35%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 17 hr
  2. washwashed with water
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
  6. additionN,N′-Carbonyldiimidazole (58 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (55 mg) were added
  7. stirringthe mixture was stirred at room temperature for 15 hr
  8. additionThe reaction mixture was diluted with ethyl acetate
  9. washwashed with saturated aqueous potassium hydrogensulfate solution
  10. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=10/90→30/70 (volume ratio)]
  13. customcrystallized from acetonitrile

Sources & evidence

ORD record
ord-d8d7ba5bc3434b0a8e1c14c926a0f1e4
Source dataset
uspto-grants-2012_10
Patent number
US08283353B2

Reaction notes

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