Potassium Carbonate → HCID 178432322, compound

HRID 220781Notes

Reaction equation

HRID 220781 reaction equation
[C:1]([N:9]1[CH2:15][CH2:14][CH:13](Br)[C:12](=[O:17])[C:11]2[CH:18]=[CH:19][CH:20]=[CH:21][C:10]1=2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:23]([NH2:26])(=[NH:25])[CH3:24].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([N:9]1[CH2:15][CH2:14][C:13]2[N:26]=[C:23]([CH3:24])[NH:25][C:12]=2[C:11]2[CH:18]=[CH:19][CH:20]=[CH:21][C:10]1=2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:1]([N:9]1[CH2:15][CH2:14][C:13]2[N:25]=[C:23]([CH3:24])[O:17][C:12]=2[C:11]2[CH:18]=[CH:19][CH:20]=[CH:21][C:10]1=2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium Carbonate3×HCID 67170Acetamidine monohydrochloride3×HCID 231123501-Benzoyl-4-bromo-1,2,3,4-tetrahydro-benzo[b]azepin-5-one

Product 2

HCID 231123696-benzoyl-2-methyl-5,6-dihydro-4H-1-oxa-3,6-diaza-benzo[e]azuleneYield 4%HCID 178432322HCID 178432322, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-Benzoyl-4-bromo-1,2,3,4-tetrahydro-benzo[b]azepin-5-one (67.5 g, 200 mmol) from Example E5.7, acetamidine hydrochloride (92.7 g, 980 mmol) and potassium carbonate (136.0 g, 980 mmol) were suspended in acetonitrile (2.0 liters) and heated at reflux for 17 h under nitrogen. Additional acetamidine hydrochloride (18.5 g, 200 mmol) and potassium carbonate (27.7 g, 200 mmol) were added and the reaction mixture was heated at reflux for a further 6 h. Additional acetamidine hydrochloride (18.5 g, 200 mmol) and potassium carbonate (27.7 g, 200 mmol) were added again and the reaction mixture was heated at reflux for a further 6 h. On cooling to room temperature, the reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was taken up in dichloromethane (1.4 liters), washed with water (500 ml), dried over sodium sulfate, filtered and reduced in vacuo. The crude products were purified by flash chromatography on silica gel (eluant; 45% EtOAc:45% acetonitrile: 10% methanol) to yield the title compound (26.7 g, 34%) and 6-benzoyl-2-methyl-5,6-dihydro-4H-1-oxa-3,6-diaza-benzo[e]azulene (3.3 g, 4%).

Workup

  1. temperatureheated
  2. temperatureat reflux for 17 h under nitrogen
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for a further 6 h
  5. temperaturethe reaction mixture was heated
  6. temperatureat reflux for a further 6 h
  7. filtrationthe reaction mixture was filtered
  8. concentrationthe filtrate was concentrated in vacuo
  9. washwashed with water (500 ml)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customThe crude products were purified by flash chromatography on silica gel (eluant; 45% EtOAc:45% acetonitrile: 10% methanol)

Sources & evidence

ORD record
ord-40ee044daf72473a993137e1df243929
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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