Phosphorus oxychloride → [2-Chloro(3-chlorophenyl)-6-quinazolinyl](4-methylphenyl)-methanone

HRID 1788061Notes

Reaction equation

HRID 1788061 reaction equation
[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:26])[C:19]4[CH:24]=[CH:23][C:22]([CH3:25])=[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:30])=O>>[Cl:30][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]([CH3:25])=[CH:21][CH:20]=3)=[O:26])[CH:16]=2)[N:11]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 686874324-(3-chlorophenyl)-6-(4-methylbenzoyl)-2(1H)-quinazolinone

Product 1

HCID 17976110[2-Chloro(3-chlorophenyl)-6-quinazolinyl](4-methylphenyl)-methanoneYield 70%

Conditions

Temperature
100 °C

Procedure

A mixture of intermediate 22 (0.041 mol) in phosphoryl chloride (105 ml) was stirred at 100° C. for 4 hours then cooled. The solvent was evaporated. The residue was taken up DCM. The solvent was evaporated. The residue was taken up in DCM. The mixture was poured out into ice water, basified with K2CO3 10% and extracted. 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, yielding 11.4 g (70%) of intermediate 23. The mother layer was evaporated and purified by column chromatography over silica gel (eluent: cyclohexane/EtOAc; 90/10; 15-40 μm). The pure fractions were collected and the solvent was evaporated, yielding 1.7 g (10.5%) of [2-chloro-4-(3-chlorophenyl)-6-quinazolinyl](4-methylphenyl)-methanone (intermediate 23), mp. 156° C.

Workup

  1. temperaturethen cooled
  2. customThe solvent was evaporated
  3. customThe solvent was evaporated
  4. additionThe mixture was poured out into ice water
  5. extractionextracted
  6. customThe organic layer was separated
  7. washwashed with water
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent was evaporated
  11. customThe residue was crystallized from CH3CN
  12. filtrationThe precipitate was filtered off
  13. customdried

Sources & evidence

ORD record
ord-bd8f502824d94ebf940f9a1a526c49ba
Source dataset
uspto-grants-2009_03
Patent number
US07511138B2

Reaction notes

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