Dimethyl Sulfoxide → HCID 178438448, compound

HRID 520108Notes

Reaction equation

HRID 520108 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH3:13][N:14]([CH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1)[C@H:15]1[CH2:20][CH2:19][C@H:18]([N:21]2[C:26](=[O:27])[C:25]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[C:36]([C:41]#[N:42])=[CH:37][CH:38]=[CH:39][CH:40]=4)=[CH:31][CH:30]=3)=[C:24]([CH2:43][CH2:44][CH3:45])[N:23]3[N:46]=[CH:47][N:48]=[C:22]23)[CH2:17][CH2:16]1>O.C(OCC)(=O)C>[CH3:13][N:14]([CH:49]1[CH2:50][CH2:51][O:52][CH2:53][CH2:54]1)[C@H:15]1[CH2:16][CH2:17][C@H:18]([N:21]2[C:26](=[O:27])[C:25]([CH2:28][C:29]3[CH:30]=[CH:31][C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[C:41]4[NH:3][C:4](=[O:7])[O:5][N:42]=4)=[CH:33][CH:34]=3)=[C:24]([CH2:43][CH2:44][CH3:45])[N:23]3[N:46]=[CH:47][N:48]=[C:22]23)[CH2:19][CH2:20]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HCl2×HCID 516892Sodium Bicarbonate2×HCID 178438577HCID 178438577, compound

Product 1

HCID 178438448HCID 178438448, compoundYield 30.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.24 g), sodium hydrogen carbonate (0.40 g) and dimethyl sulfoxide (3 mL) was stirred at 40° C. for 30 min, 4′-[(4-{trans-4-[methyl(tetrahydro-2H-pyran-4-yl)amino]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.13 g) was added, and the mixture was stirred at 90° C. for 16 hr. Hydroxylammonium chloride (0.24 g) and sodium hydrogen carbonate (0.40 g) were added, and the mixture was further stirred at 90° C. for 6 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 (0.046 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.043 mL) were 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 7 with 1 M hydrochloric acid and 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 (0.044 g, 29%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. stirringthe mixture was further stirred at 90° C. for 6 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. dissolutionthe residue was dissolved in tetrahydrofuran (2 mL)
  8. additionN,N′-Carbonyldiimidazole (0.046 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.043 mL) were added
  9. stirringthe mixture was stirred at room temperature for 20 hr
  10. additionEthyl acetate and water were added to the reaction mixture
  11. extractionextracted with ethyl acetate
  12. washThe organic layer was washed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customThe solvent was evaporated under reduced pressure
  15. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ada718ee5e2747468175f3587f206e65
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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