Sodium Hydroxide → HCID 21865172, compound

HRID 858982Notes

Reaction equation

HRID 858982 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15](Cl)[N:14]=[CH:13][N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[CH:22]2.[OH-].[Na+]>O1CCOCC1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[CH:13][N:14]=[C:15]([O:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[NH:24][CH:23]=[CH:22]4)[CH:16]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 160545-HydroxyindoleHCID 16749212HCID 16749212, compound

Product 1

HCID 21865172HCID 21865172, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a 100-mL, round-bottomed flask containing 4-(4-tert-butyl-phenyl)-6-chloro-pyrimidine, (Example 1(a)), (0.15 g, 0.61 mmol) and 5-hydroxyindole (0.24 g, 1.8 mmol, Aldrich) in 1,4-dioxane (12 mL), was added NaOH (8.0 mL, 8.0 mmol, 1.0 N). The mixture was heated at reflux for 4 h, and after cooling to room temperature, the solvent was removed in vacuum. EtOAc (15 mL) was added to the residue, and the organic layer was washed with 1 N NaOH (10 mL), water (10 mL), dried over Na2SO4, filtered, and concentrated in vacuum. After purifying the crude product by silica gel chromatography (4:1 hexanes/EtOAc), the resulting solid was dissolved in acetone (3 mL). Water (5 mL) was added dropwise to this mixture, and a white precipitate fell out of solution, which was collected by filtration, washed with water (0.5 mL), and dried under vacuum at 50° C. for 48 h to furnish the title compound. Mp: 143–145° C. MS (ESI, pos. ion) m/z: 344 (M+1). Anal. Calcd for C22H21N3O.(H2O)1/8: C, 76.44; H, 6.20; N, 12.16. Found: C, 76.63; H, 6.20; N, 12.12.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 h
  3. customthe solvent was removed in vacuum
  4. additionEtOAc (15 mL) was added to the residue
  5. washthe organic layer was washed with 1 N NaOH (10 mL), water (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuum
  9. customAfter purifying the crude product by silica gel chromatography (4:1 hexanes/EtOAc)
  10. dissolutionthe resulting solid was dissolved in acetone (3 mL)
  11. additionWater (5 mL) was added dropwise to this mixture
  12. filtrationwas collected by filtration
  13. washwashed with water (0.5 mL)
  14. customdried under vacuum at 50° C. for 48 h

Sources & evidence

ORD record
ord-8e7499888e1f470cab08883eeae5ca61
Source dataset
uspto-grants-2006_12
Patent number
US07148221B2

Reaction notes

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