Thionyl Chloride → 4-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride

HRID 634698Notes

Reaction equation

HRID 634698 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)([Cl:24])=O.Br[C:27]1[C:33]([OH:34])=[CH:32][C:30]([NH2:31])=[C:29]([F:35])[CH:28]=1>CN(C=O)C.C(O)(C)C.CC(C)=O>[ClH:24].[Cl:24][C:27]1[C:33]([OH:34])=[CH:32][C:30]([NH:31][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][N:7]=2)=[C:29]([F:35])[CH:28]=1

Participants

7

Reactant 3

HCID 24386Thionyl ChlorideHCID 109656515-Amino-2-bromo-4-fluorophenolHCID 1354756166-Methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 867563544-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochlorideYield 83%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 180AcetoneSolventHCID 3776IsopropanolSolvent

Procedure

A mixture of 6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one (260 mg, 0.90 mmol), thionyl chloride (5 ml) and DMF (2 drops) was heated at reflux for 45 minutes and allowed to cool. The excess thionyl chloride was removed by evaporation, and the residue azeotroped with toluene. A solution of 4-chloro-2-fluoro-5-hydroxyaniline (160 mg, 1.0 mmol), (as described in EP 61741 A2), in isopropanol (5 ml) was added to the residue and the mixture was heated at reflux for 1 hour and then allowed to cool. The mixture was diluted with acetone, and the solid product collected by filtration, washed with acetone and dried to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride(381 mg, 83%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 45 minutes
  3. temperatureto cool
  4. customThe excess thionyl chloride was removed by evaporation
  5. customthe residue azeotroped with toluene
  6. temperaturethe mixture was heated
  7. temperatureat reflux for 1 hour
  8. temperatureto cool
  9. filtrationthe solid product collected by filtration
  10. washwashed with acetone
  11. customdried

Sources & evidence

ORD record
ord-9282a78c67684690960822e4c92d5785
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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