Triethylamine → N-(5-Chlorobenzo[d][1,3]dioxol-4-yl)-5,7-difluoroquinazolin-4-amine

HRID 1873647Notes

Reaction equation

HRID 1873647 reaction equation
C(O)(=O)C.[CH:5](N)=[NH:6].[Cl:8][C:9]1[C:14]([NH:15][C:16](=[NH:26])[C:17]2[C:22](F)=[CH:21][C:20]([F:24])=[CH:19][C:18]=2[F:25])=[C:13]2[O:27][CH2:28][O:29][C:12]2=[CH:11][CH:10]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[Cl:8][C:9]1[C:14]([NH:15][C:16]2[C:17]3[C:22](=[CH:21][C:20]([F:24])=[CH:19][C:18]=3[F:25])[N:6]=[CH:5][N:26]=2)=[C:13]2[O:27][CH2:28][O:29][C:12]2=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 160693Formamidine acetate2×HCID 178512059N1-(6-chloro-2,3-methylenedioxyphenyl)-2,4,6-trifluorobenzamidine

Product 1

HCID 11695717N-(5-Chlorobenzo[d][1,3]dioxol-4-yl)-5,7-difluoroquinazolin-4-amine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Formamidine acetic acid salt (0.185 g) was added to a stirred solution of N1-(6-chloro-2,3-methylenedioxyphenyl)-2,4,6-trifluorobenzamidine (0.204 g) in toluene (5 ml) and the reaction mixture was heated to reflux for 16 hours. A second portion (0.185 g) of formamidine acetic acid salt was added and the reaction mixture was heated to reflux for a further 16 hours. Triethylamine (0.25 ml) was added and the reaction mixture was heated to reflux for a further 3 days. The resultant reaction mixture was cooled to ambient temperature and partitioned between methylene chloride (25 ml) and a saturated aqueous sodium bicarbonate solution (25 ml). The organic solution was washed with 10% aqueous citric acid (25 ml), dried over magnesium sulphate and evaporated. The resultant oil was purified by column chromatography on silica gel using increasingly polar mixtures of isohexane and ethyl acetate as eluent. There was thus obtained 4-(6-chloro-2,3-methylenedioxyanilino)-5,7-difluoroquinazoline (0.068 g).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 16 hours
  3. temperaturethe reaction mixture was heated
  4. temperatureto reflux for a further 16 hours
  5. temperaturethe reaction mixture was heated
  6. temperatureto reflux for a further 3 days
  7. customThe resultant reaction mixture
  8. custompartitioned between methylene chloride (25 ml)
  9. washThe organic solution was washed with 10% aqueous citric acid (25 ml)
  10. dry with materialdried over magnesium sulphate
  11. customevaporated
  12. customThe resultant oil was purified by column chromatography on silica gel using
  13. temperatureincreasingly polar mixtures of isohexane and ethyl acetate as eluent

Sources & evidence

ORD record
ord-28e37cc266084a22b6c54d7ea33c8380
Source dataset
uspto-grants-2012_11
Patent number
US08304417B2

Reaction notes

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