Phosphorus oxychloride → [2-Chloro-4-(3-chlorophenyl)-6-quinazolinyl](4-methoxyphenyl)-methanone
Reaktionsgleichung
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18](=[O:27])[C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)[CH:16]=3)[NH:11][C:10](=O)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.P(Cl)(Cl)([Cl:31])=O>>[Cl:31][C:10]1[N:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:27])[CH:16]=2)[N:11]=1Komponenten
3
Reaktionsbedingungen
- Temperatur
- 100 °C
Versuchsvorschrift
Intermediate 13 (0.0432 mol) was added at room temperature to phosphoryl chloride (150 ml). The mixture was stirred at 100° C. for 3 hours then brought to room temperature. The solvent was evaporated till dryness. The residue was taken up in DCM. The solvent was evaporated. The residue was taken up in DCM. The mixture was poured out into ice water, neutralized with K2CO3 solid and extracted with DCM. The organic layer was separated, washed with water, dried (MgSO4), filtered and the solvent was evaporated. The residue was crystallized from CH3CN. The precipitate was filtered off and dried under a vacuo, yielding 15.5 g (87%) of intermediate 14. The mother layer was purified by column chromatography over silica gel (eluent: toluene/EtOAc; 93/7; 15-40 μm). The pure fractions were collected and the solvent was evaporated. The residue (0.7 g, 4%) was crystallized from 2-propanone. The precipitate was filtered off and dried under a vacuo, yielding 0.5 g (3%) of [2-chloro-4-(3-chlorophenyl)-6-quinazolinyl](4-methoxyphenyl)-methanone (intermediate 14), mp. 175° C.