Dimethyl-p-toluidine → 6-Chloro-8-methoxy-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic Acid Ethyl Ester

HRID 351831Notes

Reaction equation

HRID 351831 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:15]=1[CH2:14][NH:13][C:12](=O)[C:11]1[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:10]2=1)=[O:5])[CH3:2].CN(C)C1C=CC(C)=CC=1.[Cl-:33].[P+]=O>ClC1C=CC=CC=1.C(Cl)Cl.CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:15]=1[CH2:14][N:13]=[C:12]([Cl:33])[C:11]1[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:10]2=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 7471Dimethyl-p-toluidineHCID 699216568-Methoxy-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic Acid Ethyl EsterHCID 178527006HCID 178527006, compound

Product 1

HCID 699215836-Chloro-8-methoxy-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic Acid Ethyl Ester

Reagents, catalysts & solvents 2

HCID 7964ChlorobenzeneSolventHCID 21584124Propan-2-one--dichloromethane (1/1)Solvent

Procedure

8-Methoxy-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester (7.5 g, 25 mmol) and N,N-dimethyl-p-toluidine (10.8 mL, 75 mmol) were mixed in chlorobenzene (80 mL) under argon. Phosphorous oxide chloride (3.4 mL, 37 mmol) was added at rt, and the mixture heated at reflux for 3.5 h. The resulting solution was cooled to rt, diluted with CH2Cl2/aceton 100:15 (300 mL), and directly purified by flash chromatography on silica gel in CH2Cl2/acetone 100:15. The white product was recrystallized by dissolution in hot ethyl acetate (300 mL), concentrated until precipitation started (ca. 100 mL). Yield: 7 g (88%). mp 186° C. m/z 301 (M).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 3.5 h
  3. customdirectly purified by flash chromatography on silica gel in CH2Cl2/acetone 100:15
  4. customThe white product was recrystallized by dissolution in hot ethyl acetate (300 mL)
  5. concentrationconcentrated until precipitation

Sources & evidence

ORD record
ord-294698eb2e074a2e9bb7eec53d2d0381
Source dataset
uspto-grants-2004_06
Patent number
US06743789B2

Reaction notes

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