Triethylamine → 4-(3,6-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzonitrile

HRID 220957Notes

Reaction equation

HRID 220957 reaction equation
CC1[O:11][C:10]2[C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3NCCC=2N=1.S(Cl)(Cl)=O.[CH3:20][N:21]1[C:30]2[NH:29][C:28]3[CH:31]=[C:32]([CH3:35])[CH:33]=[CH:34][C:27]=3[NH:26][CH2:25][C:24]=2[CH:23]=[N:22]1.C([N:38]([CH2:41][CH3:42])CC)C>C1(C)C=CC=CC=1.ClCCl>[CH3:20][N:21]1[C:30]2[NH:29][C:28]3[CH:31]=[C:32]([CH3:35])[CH:33]=[CH:34][C:27]=3[N:26]([C:10]([C:9]3[CH:12]=[CH:13][C:42]([C:41]#[N:38])=[C:15]([CH3:14])[CH:8]=3)=[O:11])[CH2:25][C:24]=2[CH:23]=[N:22]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 231123652-methyl-5,6-dihydro-4H-benzo[b]oxazolo[5,4-d]azepineHCID 1357360353,6-Dimethyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene

Product 1

HCID 1357360404-(3,6-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzonitrileYield 85%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-cyano-3-methyl-benzoic acid from Example E6 (753 mg, 4.7 mmol) and thionyl chloride (1.02 ml, 14.0 mmol) in toluene (50 ml) was heated at reflux for 2 h. After cooling at room temperature, solvents were re-moved in vacuo and azeotroped with toluene. The residue was redissolved in dichloromethane (45 ml) and a solution of 3,6-dimethyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E2 (11.0 g, 4.7 mmol) in dichloromethane (5 ml) and triethylamine (1.3 ml, 9.3 mmol) was added slowly. The mixture was stirred at room temperature for 20 h, washed with brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel through an isolute (eluant; EtOAc) to yield the title compound (1.42 g, 85%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. customazeotroped with toluene
  4. dissolutionThe residue was redissolved in dichloromethane (45 ml)
  5. washwashed with brine
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel through an isolute (eluant; EtOAc)

Sources & evidence

ORD record
ord-3ca72dc839004bcdba630ed3dd0dc1a2
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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