Toluene → 4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline
Reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.CN(C=O)C.C1(C)C=CC=CC=1.S(Cl)([Cl:38])=O>>[Cl:38][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1Participants
5
Procedure
A solution of 4-hydroxy-6-methoxy-7-(3-morpholinopropoxy)quinazoline (2.87 g, 9 mmol) and DMF (1 ml) in thionyl chloride (35 ml) was refluxed for 45 minutes. After addition of toluene, the volatiles were removed by evaporation. The residue was partitioned between ethyl acetate and water and the aqueous layer was adjusted to pH8 with 2M aqueous sodium hydroxide. The organic layer was washed with water and brine, dried (MgSO4) and the volatiles were removed by evaporation. The solid residue was purified by column chromatography eluting with a mixture of methylene chloride, acetonitrile and methanol (50/47.5/2.5) to give 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (2 g, 66%).
Workup
- customthe volatiles were removed by evaporation
- customThe residue was partitioned between ethyl acetate and water
- washThe organic layer was washed with water and brine
- dry with materialdried (MgSO4)
- customthe volatiles were removed by evaporation
- customThe solid residue was purified by column chromatography
- washeluting with a mixture of methylene chloride, acetonitrile and methanol (50/47.5/2.5)
Sources & evidence
- ORD record
- ord-388f0d8624944a8a89f1c801f19366a8
- Source dataset
- uspto-grants-2001_02
- Patent number
- US06184225B2
Reaction notes
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