Ammonia → 4-(3-Hydroxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride

HRID 1596256Notes

Reaction equation

HRID 1596256 reaction equation
N.C([O:5][C:6]1[CH:7]=[C:8]([CH:27]=[CH:28][C:29]=1[CH3:30])[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][O:25][CH3:26])=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1)(=O)C.[Cl:31]C(Cl)Cl>CO>[ClH:31].[OH:5][C:6]1[CH:7]=[C:8]([CH:27]=[CH:28][C:29]=1[CH3:30])[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][O:25][CH3:26])=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 6212ChloroformHCID 224782334-(3-Acetoxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 217015744-(3-Hydroxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochlorideYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Concentrated aqueous ammonia (8 ml) was added to a solution of 4-(3-acetoxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline (2.38 g, 6 mmol) in a mixture of trichloromethane (24 ml) and methanol (24 ml). The mixture was heated at reflux for 8 hours and the volatiles removed by evaporation. The residue was triturated with water, the resulting solid was collected by filtration and recrystallised from methylene chloride/ethanol. The product was redissolved in a mixture of methylene chloride/ethanol and a saturated solution of hydrogen chloride in ethanol was added. The solvent was partially removed by evaporation and the mixture cooled. The resulting precipitate was collected by filtration washed with ether and dried under vacuum to give 4-(3-hydroxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (1.68 g, 80%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 8 hours
  3. customthe volatiles removed by evaporation
  4. customThe residue was triturated with water
  5. filtrationthe resulting solid was collected by filtration
  6. customrecrystallised from methylene chloride/ethanol
  7. dissolutionThe product was redissolved in a mixture of methylene chloride/ethanol
  8. additiona saturated solution of hydrogen chloride in ethanol was added
  9. customThe solvent was partially removed by evaporation
  10. temperaturethe mixture cooled
  11. filtrationThe resulting precipitate was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-1ce94f9d029c4754abcc8924fbc2fb75
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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