Dimethyl Sulfoxide → HCID 178438451, compound

HRID 520105Notes

Reaction equation

HRID 520105 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[OH:13][C:14]([C:17]1[CH:57]=[CH:56][C:20]([O:21][C@H:22]2[CH2:27][CH2:26][C@H:25]([N:28]3[C:33](=[O:34])[C:32]([CH2:35][C:36]4[CH:41]=[CH:40][C:39]([C:42]5[C:43]([C:48]#[N:49])=[CH:44][CH:45]=[CH:46][CH:47]=5)=[CH:38][CH:37]=4)=[C:31]([CH2:50][CH2:51][CH3:52])[N:30]4[N:53]=[CH:54][N:55]=[C:29]34)[CH2:24][CH2:23]2)=[CH:19][CH:18]=1)([CH3:16])[CH3:15]>O.C(OCC)(=O)C>[OH:13][C:14]([C:17]1[CH:57]=[CH:56][C:20]([O:21][C@H:22]2[CH2:27][CH2:26][C@H:25]([N:28]3[C:33](=[O:34])[C:32]([CH2:35][C:36]4[CH:41]=[CH:40][C:39]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=5[C:48]5[NH:3][C:4](=[O:7])[O:5][N:49]=5)=[CH:38][CH:37]=4)=[C:31]([CH2:50][CH2:51][CH3:52])[N:30]4[N:53]=[CH:54][N:55]=[C:29]34)[CH2:24][CH2:23]2)=[CH:19][CH:18]=1)([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HCl2×HCID 516892Sodium Bicarbonate2×HCID 178438581HCID 178438581, compound

Product 1

HCID 178438451HCID 178438451, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.29 g), sodium hydrogen carbonate (0.47 g) and dimethyl sulfoxide (3 mL) was stirred at 40° C. for 30 min, 4′-[(4-{trans-4-[4-(1-hydroxy-1-methylethyl)phenoxy]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.17 g) was added, and the mixture was stirred at 90° C. for 16 hr. Hydroxylammonium chloride (0.097 g) and sodium hydrogen carbonate (0.15 g) were further added, and the mixture was stirred at 90° C. for 4 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 (1 mL). N,N′-Carbonyldiimidazole (0.050 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.046 mL) were added, and the mixture was stirred at room temperature for 2 hr. N,N′-Carbonyldiimidazole (0.050 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.046 mL) were further added, and the mixture was stirred at room temperature for 16 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was acidified 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 and recrystallized (ethyl acetate-hexane) to give the title compound as a colorless solid (0.087 g, 47%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. stirringthe mixture was stirred at 90° C. for 4 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 (1 mL)
  8. additionN,N′-Carbonyldiimidazole (0.050 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.046 mL) were added
  9. stirringthe mixture was stirred at room temperature for 2 hr
  10. additionN,N′-Carbonyldiimidazole (0.050 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.046 mL) were further added
  11. stirringthe mixture was stirred at room temperature for 16 hr
  12. additionEthyl acetate and water were added to the reaction mixture
  13. extractionextracted with ethyl acetate
  14. washThe organic layer was washed with saturated brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customThe solvent was evaporated under reduced pressure
  17. customthe residue was purified by silica gel column chromatography
  18. customrecrystallized (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-08123dde117d40c2a1da485f287c8c16
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

Loading…