2,3-Butanediol → HCID 178438617, compound

HRID 519681Notes

Reaction equation

HRID 519681 reaction equation
[O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][N:28]=[C:4]2[N:3]1[CH:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]1.[CH3:36][CH:37]([OH:41])[CH:38](O)[CH3:39].[CH3:42]C1C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[OH:41][C:37]([CH3:42])([CH3:36])[CH:38]([CH3:39])[O:35][C@H:32]1[CH2:31][CH2:30][C@H:29]([N:3]2[C:2](=[O:1])[C:7]([CH2:8][C:9]3[CH:10]=[CH:11][C:12]([C:15]4[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=4)=[CH:13][CH:14]=3)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]3[N:26]=[CH:27][N:28]=[C:4]23)[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 2622,3-ButanediolHCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 670088534'-{[5-Oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 178438617HCID 178438617, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 4′-{[5-oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (1.0 g), butane-2,3-diol (0.38 g), 4-methylbenzenesulfonic acid (0.042 g) and toluene (20 mL) was heated with a Dean-Stark apparatus under reflux for 9 hr. The reaction mixture was added to saturated aqueous sodium hydrogen carbonate solution, 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 (20 mL), sodium cyanoborohydride (0.67 g) and boron trifluoride etherate (1.3 mL) were added, and the mixture was heated under reflux for 7 hr. The reaction mixture was added to saturated aqueous sodium hydrogen carbonate solution, 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. 60% of the residue was dissolved in acetonitrile (3 mL), Dess-Martin periodinane (1.0 g) was added, and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate solution and aqueous sodium thiosulfate solution were added to the reaction mixture, and the mixture was stirred for 1 hr. The solvent was evaporated under reduced pressure, and the residue 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 (3 mL), methylmagnesium bromide (1.9 mL, 1.0 M tetrahydrofuran solution) was added dropwise at 0° C., and the mixture was stirred at room temperature for 18 hr. The reaction mixture was added to 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 racemate (0.19 g, 27%).

Workup

  1. temperaturewas heated with a Dean-Stark apparatus
  2. temperatureunder reflux for 9 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 (20 mL)
  8. additionsodium cyanoborohydride (0.67 g) and boron trifluoride etherate (1.3 mL) were added
  9. temperaturethe mixture was heated
  10. temperatureunder reflux for 7 hr
  11. additionThe reaction mixture was added to saturated aqueous sodium hydrogen carbonate solution
  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. dissolution60% of the residue was dissolved in acetonitrile (3 mL)
  17. additionDess-Martin periodinane (1.0 g) was added
  18. additionSaturated aqueous sodium hydrogen carbonate solution and aqueous sodium thiosulfate solution were added to the reaction mixture
  19. stirringthe mixture was stirred for 1 hr
  20. customThe solvent was evaporated under reduced pressure
  21. extractionthe residue was extracted with ethyl acetate
  22. washThe organic layer was washed with saturated brine
  23. dry with materialdried over anhydrous magnesium sulfate
  24. customThe solvent was evaporated under reduced pressure
  25. dissolutionthe residue was dissolved in tetrahydrofuran (3 mL)
  26. additionmethylmagnesium bromide (1.9 mL, 1.0 M tetrahydrofuran solution) was added dropwise at 0° C.
  27. stirringthe mixture was stirred at room temperature for 18 hr
  28. additionThe reaction mixture was added to 1 M hydrochloric acid
  29. extractionthe mixture was extracted with ethyl acetate
  30. washThe organic layer was washed with saturated brine
  31. dry with materialdried over anhydrous magnesium sulfate
  32. customThe solvent was evaporated under reduced pressure
  33. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0c6c043b379c4067ae3e983a2ad1cc8f
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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