Boron tribromide → HCID 59218381, compound

HRID 2246471Notes

Reaction equation

HRID 2246471 reaction equation
C([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:16](=[O:29])[N:17]([CH3:28])[C:18]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:19][CH:20]=2)=[N:13][CH:14]=1)C1C=CC=CC=1.B(Br)(Br)Br>C(Cl)Cl.O>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:16](=[O:29])[N:17]([CH3:28])[C:18]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:19][CH:20]=2)=[N:13][CH:14]=1

Participants

5

Reactant 2

HCID 25134Boron tribromide2×HCID 59218357HCID 59218357, compound

Product 1

HCID 59218381HCID 59218381, compoundYield 77.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

5-(5-(benzyloxy)pyridin-2-yl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (1.8 g, 4.8 mmol) was dissolved in DCM (30 ml) and BBr3 (1.0 M in DCM, 6.0 ml, 6.0 mmol) was added, causing solid to form. The reaction stirred at room temperature (flask in water bath) under nitrogen. After 1 hour, more BBr3 (1 M in DCM, 6.0 ml, 6.0 mmol) was added, and stirring was continued. When LCMS analysis indicated the product had formed, the reaction was quenched with saturated sodium bicarbonate (50 ml) and the flask put in a water bath and stirred. After about 30 minutes, the layers were separated, using MeOH to help dissolve the solid material suspended in the organic layer. The aqueous phase was extracted exhaustively with 5:1 DCM/MeOH and 4:1 DCM/MeOH). Some water remained in organic phase, so these layers were separated. This aqueous phase was extracted with 10:1 DCM/MeOH (3×75 ml). All of the organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and washed with hexanes, 1:1 hexanes/Et2O, and Et2O, Solid dissolved in 1N NaOH and this basic, aqueous phase was washed with DCM to remove impurities. The pH of the aqueous phase was lowered to 7 with concentrated HCl and 10% HCl. This aqueous phase was extracted exhaustively with 10:1 and then 5:1 DCM/MeOH. The organic extracts were combined and concentrated. These were combined with residual solid obtained after neutralizing aqueous phase. The material was concentrated and put on high vac overnight to afford the desired product 5-(5-hydroxypyridin-2-yl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (1.1 g, 3.7 mmol, 77% yield). MS (ESI pos. ion) m/z: 295 (MH+). Calc'd exact mass for C16H14N4O2: 294.

Workup

  1. customto form
  2. customhad formed
  3. customthe reaction was quenched with saturated sodium bicarbonate (50 ml)
  4. customthe flask put in a water bath
  5. stirringstirred
  6. waitAfter about 30 minutes
  7. customthe layers were separated
  8. dissolutionto help dissolve the solid material
  9. extractionThe aqueous phase was extracted exhaustively with 5:1 DCM/MeOH and 4:1 DCM/MeOH)
  10. customwere separated
  11. extractionThis aqueous phase was extracted with 10:1 DCM/MeOH (3×75 ml)
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. washwashed with hexanes, 1:1 hexanes/Et2O, and Et2O, Solid
  16. dissolutiondissolved in 1N NaOH
  17. washthis basic, aqueous phase was washed with DCM
  18. customto remove impurities
  19. extractionThis aqueous phase was extracted exhaustively with 10:1
  20. concentrationconcentrated
  21. customobtained after neutralizing aqueous phase
  22. concentrationThe material was concentrated
  23. waitput on high vac overnight

Sources & evidence

ORD record
ord-8e4fd2bb82f341b3ac78c41b9ede0680
Source dataset
uspto-grants-2010_03
Patent number
US07687522B2

Reaction notes

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