Dimethyl Sulfoxide → HCID 178438447, compound

HRID 520107Notes

Reaction equation

HRID 520107 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[O:13]=[C:14]1[C:19]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[C:28]([C:33]#[N:34])=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:23][CH:22]=2)=[C:18]([CH2:35][CH2:36][CH3:37])[N:17]2[N:38]=[CH:39][N:40]=[C:16]2[N:15]1[C@H:41]1[CH2:46][CH2:45][C@H:44]([NH:47][CH:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[CH2:43][CH2:42]1>O.C(OCC)(=O)C>[O:7]=[C:4]1[O:5][N:3]=[C:33]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[C:24]2[CH:23]=[CH:22][C:21]([CH2:20][C:19]3[C:14](=[O:13])[N:15]([C@H:41]4[CH2:46][CH2:45][C@H:44]([NH:47][CH:48]5[CH2:53][CH2:52][O:51][CH2:50][CH2:49]5)[CH2:43][CH2:42]4)[C:16]4[N:17]([N:38]=[CH:39][N:40]=4)[C:18]=3[CH2:35][CH2:36][CH3:37])=[CH:26][CH:25]=2)[NH:34]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 178438576HCID 178438576, compound

Product 1

HCID 178438447HCID 178438447, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.47 g), sodium hydrogen carbonate (0.76 g) and dimethyl sulfoxide (2 mL) was stirred at 40° C. for 30 min, 4′-({5-oxo-7-propyl-4-[trans-4-(tetrahydro-2H-pyran-4-ylamino)cyclohexyl]-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.25 g) was added, and the mixture was stirred at 90° C. for 16 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate/2-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (1.5 mL). N,N′-Carbonyldiimidazole (0.081 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.075 mL) were added, and the mixture was stirred at room temperature for 20 hr. N,N′-Carbonyldiimidazole (0.081 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.075 mL) were further added, and the mixture was stirred at room temperature for 5 hr. N,N′-Carbonyldiimidazole (0.081 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.075 mL) were further added, and the mixture was stirred at room temperature for 20 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was adjusted to pH 6 with 1 M hydrochloric acid. The precipitate was collected by filtration and washed with methanol to give the title compound as a colorless solid (0.11 g, 41%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. extractionthe mixture was extracted with ethyl acetate/2-propanol (3/1)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in tetrahydrofuran (1.5 mL)
  6. additionN,N′-Carbonyldiimidazole (0.081 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.075 mL) were added
  7. stirringthe mixture was stirred at room temperature for 20 hr
  8. additionN,N′-Carbonyldiimidazole (0.081 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.075 mL) were further added
  9. stirringthe mixture was stirred at room temperature for 5 hr
  10. additionN,N′-Carbonyldiimidazole (0.081 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.075 mL) were further added
  11. stirringthe mixture was stirred at room temperature for 20 hr
  12. additionEthyl acetate and water were added to the reaction mixture
  13. filtrationThe precipitate was collected by filtration
  14. washwashed with methanol

Sources & evidence

ORD record
ord-0367538311a0460296fa0ec50b707d2a
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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