1-Bromo-4-fluorobenzene → HCID 44177734, compound

HRID 1890417Notes

Reaction equation

HRID 1890417 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([NH:8][CH:9]2[C:15]3=[N:16][C:17]([C:21]4[CH:26]=[CH:25][N:24]=[CH:23][N:22]=4)=[CH:18][C:19](=[O:20])[N:14]3[CH2:13][CH2:12][NH:11][CH2:10]2)=[O:7])=[C:4]([O:29][CH3:30])[CH:3]=1.Br[C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([NH:8][CH:9]2[C:15]3=[N:16][C:17]([C:21]4[CH:26]=[CH:25][N:24]=[CH:23][N:22]=4)=[CH:18][C:19](=[O:20])[N:14]3[CH2:13][CH2:12][N:11]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[CH2:10]2)=[O:7])=[C:4]([O:29][CH3:30])[CH:3]=1

Participants

8

Reactant 5

HCID 99931-Bromo-4-fluorobenzeneHCID 10340Sodium CarbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 23676156Sodium t-butoxideHCID 44195246HCID 44195246, compound

Product 1

HCID 44177734HCID 44177734, compoundYield 38.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture containing 0.035 g (0.08 mmol) of (+/−)-4-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,5,6,7,8,9-hexahydro-1,4a,7-triaza-benzocyclohepten-9-yl)-benzamide, 0.016 g (0.09 mmol) of 4-bromofluorobenzene, 0.009 g (0.10 mmol) of sodium tert-butoxide, 0.006 g (0.03 mmol) of tri-tert-butylphosphine and 0.007 g (0.01 mmol) of tris(dibenzylideneacetone)dipalladium(0) in 1.60 mL of anhydrous toluene under argon atmosphere was stirred under reflux for 4 h30. The reaction mixture was cooled, aqueous solution of sodium carbonate was added and the resulting solution extracted with dichloromethane. The combined extracts were washed with saturated aqueous sodium chloride, dried over sodium sulfate and evaporated. The crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 90/10/1 to afford 0.016 g (38%) of the pure product as a powder.

Workup

  1. temperatureunder reflux for 4 h30
  2. temperatureThe reaction mixture was cooled
  3. extractionthe resulting solution extracted with dichloromethane
  4. washThe combined extracts were washed with saturated aqueous sodium chloride
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 90/10/1

Sources & evidence

ORD record
ord-f12fb0db8cd042ee81ce49b31630929c
Source dataset
uspto-grants-2013_08
Patent number
US08507476B2

Reaction notes

Loading…