Toluene → 4-Chloro-7-methoxy-6-(3-(4-morpholinyl)propoxy)quinazoline

HRID 1597202Notes

Reaction equation

HRID 1597202 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](=O)[NH:8][CH:9]=[N:10]2)=[CH:5][C:4]=1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.CN(C=O)C.C1(C)C=CC=CC=1.S(Cl)([Cl:38])=O>>[Cl:38][C:7]1[C:6]2[C:11](=[CH:12][C:3]([O:2][CH3:1])=[C:4]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH:5]=2)[N:10]=[CH:9][N:8]=1

Participants

5

Reactant 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1353996737-Methoxy-6-(3-morpholin-4-yl-propoxy)-3H-quinazolin-4-one

Product 1

HCID 226492214-Chloro-7-methoxy-6-(3-(4-morpholinyl)propoxy)quinazolineYield 58%

Conditions

Temperature
80 °C

Procedure

A solution of 7-methoxy-6-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one (990 mg, 3.1 mmol) in thionyl chloride (10 ml) containing DMF (0.1 ml) was heated at 80° C. for 1.5 hours. After cooling, toluene was added and the solvent was removed by evaporation. The residue was triturated with ether, and the volatiles were removed by evaporation. The residue was partitioned between ethyl acetate and water and the aqueous layer was adjusted to pH7.5 with 2M sodium hydroxide. The organic layer was washed with brine, dried (MgSO4) and the volatiles removed by evaporation. The residue was purified by flash chromatography eluting with methylene chloride/methanol (1/9 followed by 95/5). The solid was triturated with hexane, collected by filtration and washed with ether to give 4-chloro-7-methoxy-6-(3-morpholinopropoxy)quinazoline (614 mg, 58%).

Workup

  1. temperatureAfter cooling
  2. customthe solvent was removed by evaporation
  3. customThe residue was triturated with ether
  4. customthe volatiles were removed by evaporation
  5. customThe residue was partitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe volatiles removed by evaporation
  9. customThe residue was purified by flash chromatography
  10. washeluting with methylene chloride/methanol (1/9 followed by 95/5)
  11. customThe solid was triturated with hexane
  12. filtrationcollected by filtration
  13. washwashed with ether

Sources & evidence

ORD record
ord-d44a03753fd6486899c7afc939cbca00
Source dataset
uspto-grants-2001_09
Patent number
US06294532B1

Reaction notes

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