Dimethyl Sulfoxide → HCID 178438518, compound

HRID 520140Notes

Reaction equation

HRID 520140 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[Si]([O:20][CH:21]([CH:58]([F:60])[F:59])[CH2:22][O:23][C@H:24]1[CH2:29][CH2:28][C@H:27]([N:30]2[C:35](=[O:36])[C:34]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([C:44]4[C:45]([C:50]#[N:51])=[CH:46][CH:47]=[CH:48][CH:49]=4)=[CH:40][CH:39]=3)=[C:33]([CH2:52][CH2:53][CH3:54])[N:32]3[N:55]=[CH:56][N:57]=[C:31]23)[CH2:26][CH2:25]1)(C(C)(C)C)(C)C>O.C(OCC)(=O)C>[F:60][CH:58]([F:59])[CH:21]([OH:20])[CH2:22][O:23][C@H:24]1[CH2:25][CH2:26][C@H:27]([N:30]2[C:35](=[O:36])[C:34]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=4[C:50]4[NH:51][C:4](=[O:7])[O:5][N:3]=4)=[CH:40][CH:39]=3)=[C:33]([CH2:52][CH2:53][CH3:54])[N:32]3[N:55]=[CH:56][N:57]=[C:31]23)[CH2:28][CH2:29]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 178438683HCID 178438683, compound

Product 1

HCID 178438518HCID 178438518, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.18 g), sodium hydrogen carbonate (0.24 g) and dimethyl sulfoxide (3 mL) was stirred at 40° C. for 30 min, 4′-({4-[trans-4-(2-{[tert-butyl(dimethyl)silyl]oxy}-3,3-difluoropropoxy)cyclohexyl]-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 21 hr. 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. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (2 mL). N,N′-Carbonyldiimidazole (0.035 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.032 mL) were added, and the mixture was stirred at room temperature for 2 hr. Thereafter, tetrabutylammonium fluoride (0.44 mL, 1.0 M tetrahydrofuran solution) was added, and the mixture was stirred at 70° C. for 2 hr. To the reaction mixture was added 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic 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 solid (0.080 g, 73%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 21 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionthe residue was dissolved in tetrahydrofuran (2 mL)
  7. additionN,N′-Carbonyldiimidazole (0.035 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.032 mL) were added
  8. stirringthe mixture was stirred at room temperature for 2 hr
  9. additionThereafter, tetrabutylammonium fluoride (0.44 mL, 1.0 M tetrahydrofuran solution) was added
  10. stirringthe mixture was stirred at 70° C. for 2 hr
  11. additionTo the reaction mixture was added 1 M hydrochloric acid
  12. extractionthe mixture was extracted with ethyl acetate
  13. washThe organic layer was washed with saturated brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customThe solvent was evaporated under reduced pressure
  16. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-deefedd6f6314968ad4b8b7d73e5c50d
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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