Hydrochloric Acid → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(2-methylthioethoxy)quinazoline

HRID 634694Notes

Reaction equation

HRID 634694 reaction equation
Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][S:18][CH3:19])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[F:20][C:21]1[CH:27]=[C:26]([CH3:28])[C:25]([OH:29])=[CH:24][C:22]=1[NH2:23]>C(O)(C)C.CC(C)=O>[F:20][C:21]1[CH:27]=[C:26]([CH3:28])[C:25]([OH:29])=[CH:24][C:22]=1[NH:23][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][S:18][CH3:19])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 101540985-Amino-4-fluoro-2-methylphenolHCID 212603184-Chloro-6-methoxy-7-(2-methylthioethoxy)quinazoline

Product 1

HCID 212603644-(2-Fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(2-methylthioethoxy)quinazolineYield 53.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3776IsopropanolSolvent

Procedure

1M Ethereal hydrogen chloride (3.1 ml, 3.1 mmol) was added to 4-chloro-6-methoxy-7-(2-methylthioethoxy)quinazoline (0.8 g, 2.8 mmol) and 2-fluoro-5-hydroxy-4-methylaniline (0.44 g, 3.12 mmol), (prepared as described for the starting material in Example 8), in isopropanol (25 ml). The mixture was heated at reflux for 2 hours, then allowed to cool. The resulting suspension was diluted with acetone and the precipitate collected by filtration and purified by column chromatography eluting with methylene chloride/methanol/ammonia (100/8/1) to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(2-methylthioethoxy)quinazoline (580 mg, 52%).

Workup

  1. custom(prepared
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 2 hours
  4. temperatureto cool
  5. filtrationthe precipitate collected by filtration
  6. custompurified by column chromatography
  7. washeluting with methylene chloride/methanol/ammonia (100/8/1)

Sources & evidence

ORD record
ord-ffad0531b72d464ea033b52619362715
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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