Hydrochloric Acid → 4-(4-Bromo-2-fluoro-5-hydroxyanilino)-6,7-dimethoxyquinazoline hydrochloride hydrate

HRID 634643Notes

Reaction equation

HRID 634643 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[Br:17][C:18]1[C:24]([OH:25])=[CH:23][C:21]([NH2:22])=[C:20]([F:26])[CH:19]=1>CC(O)CC>[OH2:13].[ClH:2].[Br:17][C:18]1[C:24]([OH:25])=[CH:23][C:21]([NH:22][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:20]([F:26])[CH:19]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 109656515-Amino-2-bromo-4-fluorophenol

Product 1

HCID 212603444-(4-Bromo-2-fluoro-5-hydroxyanilino)-6,7-dimethoxyquinazoline hydrochloride hydrateYield 168.4%

Reagents, catalysts & solvents 1

HCID 6568(+-)-2-ButanolSolvent

Procedure

Isopropanolic hydrogen chloride (0.1 ml of a 5M solution) was added to a solution of 4-chloro-6,7-dimethoxyquinazoline (202 mg, 0.9 mmol) and 4-bromo-2-fluoro-5-hydroxyaniline (as described in EP 61741 A2) (206 mg, 1 mmol) in 2-butanol (8 ml). The mixture was heated at reflux for 45 minutes, then allowed to cool. The precipitated product was collected by filtration, washed with 2-butanol, and then with ether, and dried under vacuum to give 4-(4-bromo-2-fluoro-5-hydroxyanilino)-6,7-dimethoxyquinazoline hydrochloride hydrate (340 mg, 87%) as a white solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 45 minutes
  3. temperatureto cool
  4. filtrationThe precipitated product was collected by filtration
  5. washwashed with 2-butanol
  6. dry with materialwith ether, and dried under vacuum

Sources & evidence

ORD record
ord-d7549541160e4a598cc7c867363f411e
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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