Cesium carbonate → HCID 68555663, compound

HRID 508705Notes

Reaction equation

HRID 508705 reaction equation
[Br:1][C:2]1[CH:13]=[CH:12][C:5]2[NH:6][CH2:7][CH2:8][N:9]([CH3:11])[CH2:10][C:4]=2[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:1][C:2]1[CH:13]=[CH:12][C:5]2[N:6]([C:18]3[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=3)[CH2:7][CH2:8][N:9]([CH3:11])[CH2:10][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 125101-Chloro-4-iodobenzeneHCID 685569301084743-67-8

Product 1

HCID 68555663HCID 68555663, compoundYield 21.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 7-bromo-4-methyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine (2.25 g, 9.33 mmol), 1-chloro-4-iodobenzene (3.10 g, 12.1 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-isopropyl-1,1′-biphenyl (444 mg, 0.933 mmol), and cesium carbonate (6.1 g, 18.7 mmol) in toluene (60 mL) was purged with argon for 10 minutes before palladium(II) acetate (210 mg, 0.993 mmol) was added. After purging with argon for 5 minutes, the reaction mixture was heated at reflux overnight. The mixture was cooled, partitioned with water (100 mL) and ethyl acetate (3×50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with 10:1 methylene chloride/methanol followed by rechromatography eluting with 3:1 methylene chloride/ethyl acetate to yield 7-bromo-1-(4-chlorophenyl)-4-methyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine (694 mg, 21%) as a brown foam: 1H NMR (CDCl3, 500 MHz) δ 7.45 (s, 1H), 7.37 (d, J=8.4 Hz, 1H), 7.12 (d, J=6.8 Hz, 2H), 7.01 (d, J=8.4 Hz, 1H), 6.62 (d, J=6.9 Hz, 2H), 3.71-3.67 (m, 2H), 3.60 (s, 2H), 2.88-2.85 (m, 2H), 2.36 (s, 3H); ESI MS m/z 351, 353 [M+H]+.

Workup

  1. additionwas added
  2. customAfter purging with argon for 5 minutes
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux overnight
  5. temperatureThe mixture was cooled
  6. custompartitioned with water (100 mL) and ethyl acetate (3×50 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography
  11. washeluting with 10:1 methylene chloride/methanol
  12. washeluting with 3:1 methylene chloride/ethyl acetate

Sources & evidence

ORD record
ord-af9e90dffca2493b96a4cc82b2a718d4
Source dataset
uspto-grants-2015_08
Patent number
US09096546B2

Reaction notes

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