Dimethyl Sulfoxide → HCID 178438523, compound

HRID 1412893Notes

Reaction equation

HRID 1412893 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH3:13][C:14]1([O:52][Si](CC)(CC)CC)[CH2:16][CH:15]1[O:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([N:24]2[C:29](=[O:30])[C:28]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]4[C:39]([C:44]#[N:45])=[CH:40][CH:41]=[CH:42][CH:43]=4)=[CH:34][CH:33]=3)=[C:27]([CH2:46][CH2:47][CH3:48])[N:26]3[N:49]=[CH:50][CH:51]=[C:25]23)[CH2:20][CH2:19]1>C(OCC)(=O)C>[OH:52][C@:14]1([CH3:13])[CH2:16][C@H:15]1[O:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([N:24]2[C:29](=[O:30])[C:28]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[C:44]4[NH:45][C:4](=[O:7])[O:5][N:3]=4)=[CH:34][CH:33]=3)=[C:27]([CH2:46][CH2:47][CH3:48])[N:26]3[N:49]=[CH:50][CH:51]=[C:25]23)[CH2:20][CH2:19]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 178438578HCID 178438578, compound

Product 1

HCID 178438523HCID 178438523, compoundYield 203.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of hydroxylammonium chloride (0.56 g), sodium hydrogen carbonate (0.84 g) and dimethyl sulfoxide (3.5 mL) was stirred at 50° C. for 30 min, 4′-({4-[trans-4-({2-methyl-2-[(triethylsilyl)oxy]cyclopropyl}oxy)cyclohexyl]-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.44 g) was added, and the mixture was stirred at 90° C. for 20 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then 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). N,N′-Carbonyldiimidazole (0.13 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.12 mL) were added, and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added tetrabutylammonium fluoride (1 M tetrahydrofuran solution, 1.5 mL), and the mixture was stirred at 60° C. for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated aqueous sodium hydrogen carbonate solution and 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 pale-yellow amorphous solid (0.82 g, 20%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 20 hr
  2. washwashed with water
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (3 mL)
  6. additionN,N′-Carbonyldiimidazole (0.13 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.12 mL) were added
  7. stirringthe mixture was stirred at room temperature for 1 hr
  8. additionTo the reaction mixture was added tetrabutylammonium fluoride (1 M tetrahydrofuran solution, 1.5 mL)
  9. stirringthe mixture was stirred at 60° C. for 2 hr
  10. additionThe reaction mixture was diluted with ethyl acetate
  11. washwashed with 1 M hydrochloric acid
  12. dry with materialwith saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fe8ae59ff6ef4e27b7fd934d105e153f
Source dataset
uspto-grants-2014_12
Patent number
US08921379B2

Reaction notes

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