Thionyl Chloride → HCID 21260354, compound

HRID 634689Notes

Reaction equation

HRID 634689 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][CH2:16][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)(Cl)=O.[F:28][C:29]1[CH:35]=[C:34]([CH3:36])[C:33]([OH:37])=[CH:32][C:30]=1[NH2:31]>CN(C=O)C.C(O)(C)C>[F:28][C:29]1[CH:35]=[C:34]([CH3:36])[C:33]([OH:37])=[CH:32][C:30]=1[NH:31][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 101540985-Amino-4-fluoro-2-methylphenolHCID 1354371166-Methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 21260354HCID 21260354, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 3776IsopropanolSolvent

Procedure

A mixture of 6-methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one (370 mg, 1.16 mmol), thionyl chloride (5 ml) and DMF (3 drops) was heated at reflux for 2 hours and allowed to cool. The excess thionyl chloride was removed by evaporation and the residue was azeotroped with toluene. A solution of 2-fluoro-5-hydroxy-4-methylaniline (220 mg, 1.56 mmol) in isopropanol (10 ml) was added to the solid residue and the mixture was heated at reflux for 2 hours and then allowed to cool. The resulting precipitate was collected by filtration, washed with methylene chloride and dried. The impure solid product was treated with aqueous sodium hydrogen carbonate, to give a suspension and the product was recollected by filtration and purified by column chromatography eluting with methylene chloride/methanol (9/1) to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (140 mg, 27%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperatureto cool
  4. customThe excess thionyl chloride was removed by evaporation
  5. customthe residue was azeotroped with toluene
  6. temperaturethe mixture was heated
  7. temperatureat reflux for 2 hours
  8. temperatureto cool
  9. filtrationThe resulting precipitate was collected by filtration
  10. washwashed with methylene chloride
  11. customdried
  12. additionThe impure solid product was treated with aqueous sodium hydrogen carbonate
  13. customto give a suspension
  14. filtrationthe product was recollected by filtration
  15. custompurified by column chromatography
  16. washeluting with methylene chloride/methanol (9/1)

Sources & evidence

ORD record
ord-fe04573a12d6415daf6eb9b20e5486e3
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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