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

HRID 1386283Notes

Reaction equation

HRID 1386283 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.C1(C)C=CC=CC=1.S(Cl)([Cl:33])=O>CN(C=O)C>[Cl:33][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 3

HCID 1140TolueneHCID 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%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 7-methoxy-6-(3-morpholinopropoxy)-3,4-dihydroquinazolin4-one (990 mg, 3.1 mmol) in thionyl chloride (10 ml) and DMF (0.1 ml) was heated at 80° C. for 1.5 hours. The mixture was allowed to cool, toluene was added and the solvent was 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 solution. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography eluting with methylene chloride/methanol (119 followed by 95/5). The purified 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. temperatureto cool
  2. customthe solvent was removed by evaporation
  3. customThe residue was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was purified by flash chromatography
  9. washeluting with methylene chloride/methanol (119 followed by 95/5)
  10. customThe purified solid was triturated with hexane
  11. filtrationcollected by filtration
  12. washwashed with ether

Sources & evidence

ORD record
ord-2a50218973db4b1091a46e45dc6e259c
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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