Phosphorus oxychloride → 6-[2-(2,5-Dimethoxyphenyl)ethyl]-4-chloroquinazoline
Reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][CH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][NH:17][C:16]2=O.P(Cl)(Cl)([Cl:26])=O.P(Cl)(Cl)(Cl)(Cl)Cl>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][CH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][N:17]=[C:16]2[Cl:26]Participants
Procedure
150 mg of 6-[2-(2,5-dimethoxyphenyl)ethyl]-3H-quinazolin-4-one are heated together with 5 ml of phosphorus oxychloride and 100 mg of phosphorus pentachloride at reflux for 30 minutes. The mixture is concentrated in vacuo and then partitioned between ice-cold 2 M aqueous pH 7 buffer and ethyl acetate. The organic layer is separated, dried and evaporated in vacuo to yield crude 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-chloroquinazoline, which can be directly used in the following step or purified by chromatography (silica gel, cyclohexane/ethyl acetate=1/1). The crude intermediate is added to a solution of sodium isopropoxide (prepared from 8.3 mg of sodium in 20 ml of isopropanol) in isopropanol. The mixture is refluxed for 1 hour, concentrated in vacuo and poured onto water. Extraction with ethyl acetate yields the crude title compound, which is purified by chromatography on silica gel (cyclohexane/ethyl acetate=2/1) to give a colourless oil.
Workup
- temperatureat reflux for 30 minutes
- concentrationThe mixture is concentrated in vacuo
- custompartitioned between ice-cold 2 M aqueous pH 7 buffer
- customThe organic layer is separated
- customdried
- customevaporated in vacuo
Sources & evidence
- ORD record
- ord-bc9fbe14da754a46a4a80789b91998c9
- Source dataset
- uspto-grants-1999_11
- Patent number
- US05990116
Reaction notes
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