Dimethyl Sulfoxide → HCID 178438542, compound

HRID 520082Notes

Reaction equation

HRID 520082 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[F:13][C:14]1[CH:15]=[C:16]([C:47]2[C:48]([C:53]#[N:54])=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:17]=[CH:18][C:19]=1[CH2:20][C:21]1[C:22](=[O:46])[N:23]([C@H:33]2[CH2:38][CH2:37][C@H:36]([O:39][CH:40]([CH3:45])[C:41]([OH:44])([CH3:43])[CH3:42])[CH2:35][CH2:34]2)[C:24]2[N:25]([N:30]=[CH:31][N:32]=2)[C:26]=1[CH2:27][CH2:28][CH3:29]>C(OCC)(=O)C>[F:13][C:14]1[CH:15]=[C:16]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=2[C:53]2[NH:3][C:4](=[O:7])[O:5][N:54]=2)[CH:17]=[CH:18][C:19]=1[CH2:20][C:21]1[C:22](=[O:46])[N:23]([C@H:33]2[CH2:38][CH2:37][C@H:36]([O:39][CH:40]([CH3:45])[C:41]([OH:44])([CH3:43])[CH3:42])[CH2:35][CH2:34]2)[C:24]2[N:25]([N:30]=[CH:31][N:32]=2)[C:26]=1[CH2:27][CH2:28][CH3:29]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 178438718HCID 178438718, compound

Product 1

HCID 178438542HCID 178438542, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (7.5 g), sodium hydrogen carbonate (12 g) and dimethyl sulfoxide (50 mL) was stirred at 40° C. for 30 min. 3′-Fluoro-4′-({4-[trans-4-(2-hydroxy-1,2-dimethylpropoxy)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (retention time: short, 4 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (100 mL). N,N′-Carbonyldiimidazole (1.4 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.2 mL) were successively added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with 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 amorphous solid (4 g, 91%, >99% ee).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. washwashed with water
  3. dry with materialwith brine, dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe resulting residue was dissolved in tetrahydrofuran (100 mL)
  6. additionN,N′-Carbonyldiimidazole (1.4 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.2 mL) were successively added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. additionThe reaction mixture was diluted with ethyl acetate
  9. washwashed with saturated aqueous potassium hydrogensulfate solution
  10. dry with materialwith brine, and dried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-25f0c6574546457d8f76ddf260994acb
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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