Thionyl Chloride → 4-Chloro-6-(3-chloropropoxy)-7-methoxyquinazoline

HRID 1803018Notes

Reaction equation

HRID 1803018 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[N:12]=[CH:11][NH:10][C:9]2=O.S(Cl)([Cl:21])=O>CN(C=O)C>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[N:12]=[CH:11][N:10]=[C:9]2[Cl:21]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 1355897736-(3-chloropropoxy)-7-methoxyquinazolin-4(3H)-one

Product 1

HCID 507422644-Chloro-6-(3-chloropropoxy)-7-methoxyquinazolineYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(3-chloropropoxy)-7-methoxyquinazoline-4-one (400 gm), thionyl chloride (3.2 lt) and DMF (100 ml) were refluxed for 7-8 hours. Thionyl chloride was distilled off completely under reduced pressure below 45° C. Methylene chloride (2.5 lt) and water (1.5 lt) were charged, stirred for 30 minutes at room temperature and the layers separated. The aqueous layer was extracted twice with methylene chloride (500 ml), the combined methylene chloride layer was washed with 1% sodium bicarbonate solution (1 lt), dried over sodium sulphate (20 gm) and concentrated under reduced pressure at 35-40° C. The residue was stirred with isopropyl alcohol (400 ml) at 40-45° C. for 1 hour, cooled to 0-5° C., the solids filtered, washed with chilled isopropyl alcohol (200 ml) and dried under vacuum at 45° C. to yield the title compound (406 gm, 95% yield).

Workup

  1. distillationThionyl chloride was distilled off completely under reduced pressure below 45° C
  2. additionMethylene chloride (2.5 lt) and water (1.5 lt) were charged
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted twice with methylene chloride (500 ml)
  5. washthe combined methylene chloride layer was washed with 1% sodium bicarbonate solution (1 lt)
  6. dry with materialdried over sodium sulphate (20 gm)
  7. concentrationconcentrated under reduced pressure at 35-40° C
  8. stirringThe residue was stirred with isopropyl alcohol (400 ml) at 40-45° C. for 1 hour
  9. temperaturecooled to 0-5° C.
  10. filtrationthe solids filtered
  11. washwashed with chilled isopropyl alcohol (200 ml)
  12. customdried under vacuum at 45° C.

Sources & evidence

ORD record
ord-288627ea950c4a2c8618bf12c84a24f0
Source dataset
uspto-grants-2013_01
Patent number
US08350029B2

Reaction notes

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