Dimethyl Sulfoxide → 2-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol

HRID 604125Notes

Reaction equation

HRID 604125 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:6][N:7]([C:30]1[N:35]=[CH:34][C:33](Br)=[CH:32][N:31]=1)[CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29].CS(C)=[O:48]>>[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:6][N:7]([CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29])[C:30]1[N:35]=[CH:34][C:33]([OH:48])=[CH:32][N:31]=1

Participants

3

Reactant 2

HCID 679Dimethyl SulfoxideHCID 86626868(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine

Product 1

HCID 866268722-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol

Conditions

Temperature
80 °C

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (1.06 g) is dissolved in dimethylsulfoxide (5 ml), and the mixture is degassed and thereto are added [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride (61 mg), potassium acetate (442 mg) and bis(pinacolato)diboron (571 mg). The mixture is degassed and heated to 80° C. under nitrogen flow and stirred for 45 minutes. The reaction solution is allowed to cool to room temperature, and thereto is added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed twice with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in tetrahydrofuran (5 ml), and thereto is added dropwise a 30% aqueous hydrogen peroxide solution (1.5 ml) under ice-cooling and stirred at the same temperature for 1 hour and a half. To the reaction mixture is added dropwise saturated aqueous sodium thiosulfate solution under ice-cooling, and thereto is added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=4:1→3:1) to give 2-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol (866 mg). MS (m/z): 644 [M+H]+

Workup

  1. customthe mixture is degassed
  2. additionare added [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride (61 mg), potassium acetate (442 mg) and bis(pinacolato)diboron (571 mg)
  3. customThe mixture is degassed
  4. temperatureto cool to room temperature
  5. additionis added a saturated brine
  6. extractionthe mixture is extracted with ethyl acetate
  7. washThe organic layer is washed twice with a saturated brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe resulting residue is dissolved in tetrahydrofuran (5 ml)
  11. additionis added dropwise a 30% aqueous hydrogen peroxide solution (1.5 ml) under ice-
  12. temperaturecooling
  13. stirringstirred at the same temperature for 1 hour
  14. additionTo the reaction mixture is added dropwise saturated aqueous sodium thiosulfate solution under ice-
  15. temperaturecooling
  16. additionis added a saturated brine
  17. extractionthe mixture is extracted with ethyl acetate
  18. washThe organic layer is washed with a saturated brine
  19. dry with materialdried over magnesium sulfate
  20. concentrationconcentrated under reduced pressure
  21. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=4:1→3:1)

Sources & evidence

ORD record
ord-aa4d00ea19894d3f845753909480b753
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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