Hydrochloric Acid → 4-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-morpholinoethoxy)quinazoline

HRID 634701Notes

Reaction equation

HRID 634701 reaction equation
[ClH:1].Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.Br[C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH2:29])=[C:27]([F:33])[CH:26]=1>C(O)(C)C.CC(C)=O>[Cl:1][C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH:29][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:27]([F:33])[CH:26]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 108710274-Chloro-6-methoxy-7-(2-morpholinoethoxy)quinazolineHCID 109656515-Amino-2-bromo-4-fluorophenol

Product 1

HCID 212602974-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-morpholinoethoxy)quinazolineYield 21%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3776IsopropanolSolvent

Procedure

1M Ethereal hydrogen chloride (0.72 ml, 0.72 mmol) was added to 4-chloro-6-methoxy-7-(2-morpholinoethoxy)quinazoline (210 mg, 0.65 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (115 mg, 0.71 mmol), (as described in EP 61741 A2), in isopropanol (5 ml) and the mixture heated at reflux for 2 hours and then allowed to cool. The mixture was diluted with acetone and the precipitated product collected by filtration. The impure product was dissolved in methylene chloride/ammonia (100/1) and methanol, the insolubles removed by filtration and the volatiles were removed from the filtrate by evaporation. The solid residue was washed with water and dried to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-morpholinoethoxy)quinazoline (60 mg, 21%).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 2 hours
  3. temperatureto cool
  4. filtrationthe precipitated product collected by filtration
  5. dissolutionThe impure product was dissolved in methylene chloride/ammonia (100/1)
  6. custommethanol, the insolubles removed by filtration
  7. customthe volatiles were removed from the filtrate by evaporation
  8. washThe solid residue was washed with water
  9. customdried

Sources & evidence

ORD record
ord-a00ace7c872b465196ff3fc6c42870e4
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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