Triethylamine → 4-(1-Benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-2-methyl-benzonitrile

HRID 220986Notes

Reaction equation

HRID 220986 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.C([N:22]([CH2:25][CH3:26])CC)C.[CH2:27]([N:34]1[C:43]2[C:42]3[CH:44]=[CH:45][CH:46]=[CH:47][C:41]=3[NH:40][CH2:39][CH2:38][C:37]=2[N:36]=[C:35]1[CH3:48])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1(C)C=CC=CC=1>[CH2:27]([N:34]1[C:43]2[C:42]3[CH:44]=[CH:45][CH:46]=[CH:47][C:41]=3[N:40]([C:10]([C:9]3[CH:12]=[CH:13][C:26]([C:25]#[N:22])=[C:15]([CH3:14])[CH:8]=3)=[O:11])[CH2:39][CH2:38][C:37]=2[N:36]=[C:35]1[CH3:48])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 231123652-methyl-5,6-dihydro-4H-benzo[b]oxazolo[5,4-d]azepineHCID 575554001-Benzyl-2-methyl-1,4,5,6-tetrahydro-1,3,6-triaza-benzo[e]azulene

Product 1

HCID 575552854-(1-Benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-2-methyl-benzonitrileYield 56%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 4-cyano-3-methyl-benzoic acid from Example E6 (557 mg, 3.4 mmol) and thionyl chloride (0.755 ml, 10.3 mmol) in toluene (100 ml) was heated at reflux for 2 h. After cooling to room temperature, solvents were re-moved in vacuo and azeotroped with toluene. The residue was redissolved in dichloromethane (100 ml) and triethylamine (0.962 ml, 6.9 mmol) then 1-benzyl-2-methyl-1,4,5,6-tetrahydro-1,3,6-triaza-benzo[e]azulene from Example E5a (1.0 g, 3.4 mmol) was added. The mixture was stirred at room temperature for 2 h, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 50% EtOAc:50% pet. ether then EtOAc) to yield the title compound (844 mg, 56%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. customazeotroped with toluene
  4. dissolutionThe residue was redissolved in dichloromethane (100 ml)
  5. washwashed with saturated NaHCO3
  6. dry with materialbrine, dried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (eluant

Sources & evidence

ORD record
ord-5d167ca939f1456e94e839d87befe647
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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