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

HRID 1441462Notes

Reaction equation

HRID 1441462 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: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]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 686894594-(3-chlorophenyl)-6-(4-methoxybenzoyl)-2(1H)-quinazolinone

Product 1

HCID 17976109[2-Chloro-4-(3-chlorophenyl)-6-quinazolinyl](4-methoxyphenyl)-methanoneYield 87%

Conditions

Temperature
100 °C

Procedure

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.

Workup

  1. customthen brought to room temperature
  2. customThe solvent was evaporated till dryness
  3. customThe solvent was evaporated
  4. additionThe mixture was poured out into ice water
  5. extractionextracted with DCM
  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 under a vacuo

Sources & evidence

ORD record
ord-13408a9c3f9d451aa34b17e0796f2207
Source dataset
uspto-grants-2010_02
Patent number
US07655654B2

Reaction notes

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