5-Bromo-2,4-bis(1,1-dimethylethoxy)pyrimidine → (+/-)-5-(2-Ethyl-7-methyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-2,4(1H,3H)-pyrimidinedione

HRID 324393

Reaction equation

HRID 324393 reaction equation
Br[C:2]1[C:3]([O:13]C(C)(C)C)=[N:4][C:5]([O:8]C(C)(C)C)=[N:6][CH:7]=1.C([Li])CCC.[CH2:23]([C:25]1[O:26][C:27]2[CH2:34][CH2:33][C:32]3[CH:35]=[C:36]([CH3:39])[CH:37]=[CH:38][C:31]=3[C:30](=O)[C:28]=2[N:29]=1)[CH3:24]>O1CCCC1.[Cl-].[Na+].O>[CH2:23]([C:25]1[O:26][C:27]2[CH:34]=[CH:33][C:32]3[CH:35]=[C:36]([CH3:39])[CH:37]=[CH:38][C:31]=3[CH:30]([C:2]3[C:3](=[O:13])[NH:4][C:5](=[O:8])[NH:6][CH:7]=3)[C:28]=2[N:29]=1)[CH3:24]

Participants

6

Reactant 3

HCID 8188515-Bromo-2,4-bis(1,1-dimethylethoxy)pyrimidineHCID 220036422-Ethyl-9,10-dihydro-7-methyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-oneHCID 178418339Butyllithium

Product 1

HCID 70112980(+/-)-5-(2-Ethyl-7-methyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-2,4(1H,3H)-pyrimidinedione

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of the product of step (vi) (1.74 g) in dry tetrahydrofuran (20 ml) at −78° C. was added n-butyllithium (2.3 ml of a 2.5M solution in hexanes) dropwise. After 0.5 hours a solution of the product from step (v) (1.26 g) in tetrahydrofuran (10 ml) was added. The reaction mixture was allowed to warm to room temperature and saturated brine was added. The mixture was extracted with ethyl acetate, the organic phase was dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in acetic acid (20 ml) and the solution was heated at reflux for 64 hours. The solvent was evaporated under reduced pressure and the residue was then dissolved in trifluoroacetic acid (20 ml) and the solution heated at reflux for 64 hours. The solvent was evaporated under reduced pressure. Purification was by trituration with diethyl ether and filtration.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. dry with materialthe organic phase was dried (MgSO4)
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in acetic acid (20 ml)
  5. temperaturethe solution was heated
  6. temperatureat reflux for 64 hours
  7. customThe solvent was evaporated under reduced pressure
  8. dissolutionthe residue was then dissolved in trifluoroacetic acid (20 ml)
  9. temperaturethe solution heated
  10. temperatureat reflux for 64 hours
  11. customThe solvent was evaporated under reduced pressure
  12. customPurification
  13. filtrationwas by trituration with diethyl ether and filtration

Sources & evidence

ORD record
ord-5c945cc2854e4b9c83d3d8d2b6f548bb
Source dataset
uspto-grants-2001_04
Patent number
US06218376B1

Linked notes

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