Dimethyl Sulfoxide → 4-[1-(2-hydroxyethyl)piperidin-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 520155Notes

Reaction equation

HRID 520155 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[OH:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([N:22]2[C:27](=[O:28])[C:26]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([C:36]4[C:37]([C:42]#[N:43])=[CH:38][CH:39]=[CH:40][CH:41]=4)=[CH:32][CH:31]=3)=[C:25]([CH2:44][CH2:45][CH3:46])[N:24]3[N:47]=[CH:48][N:49]=[C:23]23)[CH2:18][CH2:17]1>C(OCC)(=O)C>[OH:13][CH2:14][CH2:15][N:16]1[CH2:17][CH2:18][CH:19]([N:22]2[C:27](=[O:28])[C:26]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=4[C:42]4[NH:3][C:4](=[O:7])[O:5][N:43]=4)=[CH:32][CH:31]=3)=[C:25]([CH2:44][CH2:45][CH3:46])[N:24]3[N:47]=[CH:48][N:49]=[C:23]23)[CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 670101314'-({4-[1-(2-Hydroxyethyl)piperidin-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 1360638784-[1-(2-hydroxyethyl)piperidin-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 23%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (417 mg), sodium hydrogen carbonate (672 mg) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-({4-[1-(2-hydroxyethyl)piperidin-4-yl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (200 mg) 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 (4 mL). N,N′-Carbonyldiimidazole (81 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (76 mg) 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, and the residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=5/95→30/70 (volume ratio)] and crystallized from acetonitrile to give the title compound as colorless crystals (51 mg, 23%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 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 (4 mL)
  6. additionN,N′-Carbonyldiimidazole (81 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (76 mg) were added
  7. stirringthe mixture was stirred at room temperature for 2 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=5/95→30/70 (volume ratio)]
  13. customcrystallized from acetonitrile

Sources & evidence

ORD record
ord-72d4ae51a9bf4c10afc55df3ed0ebc2e
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

Loading…