Boron tribromide → 3-benzyl-5-(3-fluoro-4-hydroxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

HRID 2246476Notes

Reaction equation

HRID 2246476 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21]C)=[C:17]([F:23])[CH:16]=2)=[CH:11][N:10]=[C:9]1[NH:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([F:23])[CH:16]=2)=[CH:11][N:10]=[C:9]1[NH:24][C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 25134Boron tribromide2×HCID 592183673-benzyl-5-(3-fluoro-4-methoxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

Product 1

HCID 592183623-benzyl-5-(3-fluoro-4-hydroxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-benzyl-5-(3-fluoro-4-methoxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one (563.4 mg, 1.343 mmol) was suspended in DCM (12 ml) and cooled in an ice water bath. Then, BBr3 (1.0 M in DCM, 2.2 ml, 2.2 mmol) was added, and the reaction was stirred at 0 C. After 50 minutes, more BBr3 added (2.5 ml, 2.5 mmol) and stirring was continued at room temperature. After 35 minutes, the reaction was cooled to 0 C and quenched with NaOH (5 N, 2.0 ml). The pH of the solution was adjusted with 5 N HCl and saturated sodium bicarbonate to around 7, and the suspension was allowed to stand at room temperature. The suspension was then treated with 1:1 DCM/MeOH and filtered. The solid was washed with this solution and the filtrate was concentrated, treated with EtOAc, and filtered again. The solid was again washed with DCM and MeOH and filtered, and the filtrate was concentrated. This last washing and filtration sequence was repeated a few more times to remove sodium salts (NaCl; NaBr). Finally, the filtrate was concentrated and dried in vacuo to afford the desired 3-benzyl-5-(3-fluoro-4-hydroxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one, which was taken to the next step. MS (ESI pos. ion) m/z: 406 (MH+). Calc'd exact mass for C23H17F2N3O2: 405.

Workup

  1. temperaturecooled in an ice water bath
  2. stirringstirring
  3. customwas continued at room temperature
  4. waitAfter 35 minutes
  5. temperaturethe reaction was cooled to 0 C
  6. customquenched with NaOH (5 N, 2.0 ml)
  7. customto stand at room temperature
  8. additionThe suspension was then treated with 1:1 DCM/MeOH
  9. filtrationfiltered
  10. washThe solid was washed with this solution
  11. concentrationthe filtrate was concentrated
  12. additiontreated with EtOAc
  13. filtrationfiltered again
  14. washThe solid was again washed with DCM and MeOH
  15. filtrationfiltered
  16. concentrationthe filtrate was concentrated
  17. washThis last washing
  18. filtrationfiltration sequence
  19. customto remove sodium salts (NaCl; NaBr)
  20. concentrationFinally, the filtrate was concentrated
  21. customdried in vacuo

Sources & evidence

ORD record
ord-602ca7ac35be4bc5a89afd548cb61545
Source dataset
uspto-grants-2010_03
Patent number
US07687522B2

Reaction notes

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