Dimethyl Sulfoxide → 4-(4-morpholin-4-ylcyclohexyl)-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 520022Notes

Reaction equation

HRID 520022 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[N:13]1([CH:19]2[CH2:24][CH2:23][CH:22]([N:25]3[C:30](=[O:31])[C:29]([CH2:32][C:33]4[CH:38]=[CH:37][C:36]([C:39]5[C:40]([C:45]#[N:46])=[CH:41][CH:42]=[CH:43][CH:44]=5)=[CH:35][CH:34]=4)=[C:28]([CH2:47][CH2:48][CH3:49])[N:27]4[N:50]=[CH:51][N:52]=[C:26]34)[CH2:21][CH2:20]2)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1>C(OCC)(=O)C>[N:13]1([CH:19]2[CH2:24][CH2:23][CH:22]([N:25]3[C:30](=[O:31])[C:29]([CH2:32][C:33]4[CH:38]=[CH:37][C:36]([C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=5[C:45]5[NH:3][C:4](=[O:7])[O:5][N:46]=5)=[CH:35][CH:34]=4)=[C:28]([CH2:47][CH2:48][CH3:49])[N:27]4[N:50]=[CH:51][N:52]=[C:26]34)[CH2:21][CH2:20]2)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 670088404'-{[4-(4-Morpholin-4-ylcyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1360636804-(4-morpholin-4-ylcyclohexyl)-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 20%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.23 g), sodium hydrogen carbonate (0.38 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[4-(4-morpholin-4-ylcyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.12 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 (0.043 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.037 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was poured into water, and the mixture was adjusted to pH 7 with 1 N hydrochloric acid and extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.025 g, 20%).

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 (10 mL)
  6. additionN,N′-Carbonyldiimidazole (0.043 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.037 mL) were added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. additionThe reaction mixture was poured into water
  9. extractionextracted with ethyl acetate
  10. washThe obtained ethyl acetate layer was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d336fe2905eb44a89fb3751bdb271b79
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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