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

HRID 1788044ノート

反応式

HRID 1788044 の反応式
[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]([F: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]([F:25])=[CH:21][CH:20]=3)=[O:26])[CH:16]=2)[N:11]=1

参加物

3

反応物 2

HCID 24813Phosphorus oxychlorideHCID 686907514-(3-chlorophenyl)-6-(4-fluorobenzoyl)-2(1H)-quinazolinone

生成物 1

HCID 17976100[2-Chloro-4-(3-chlorophenyl)-6-quinazolinyl](4-fluorophenyl)-methanone収率 40%

反応条件

温度
100 °C

実験手順

Intermediate 5 (0.0528 mol) was added in phosphoryl chloride (200 ml) at room temperature. The mixture was stirred at 100° C. for 3 hours and cooled to room temperature. The solvent was evaporated. The residue was taken up in DCM. The solvent was evaporated till dryness. The residue was taken up in DCM, poured out into ice water, neutralised with K2CO3 solid and extracted with DCM. The organic layer was washed with water, separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue was crystallized from 2-propanone. The precipitate was filtered off and dried, yielding 8.5 g (40%) of intermediate 6. The mother layer was evaporated. The residue was purified by column chromatography over silica gel (eluent: toluene/EtOAc 95/5; 15-35 μm). The pure fractions were collected and the solvent was evaporated. A part (0.5 g) of the residue (8.9 g, 42%) was crystallized from 2-propanone. The precipitate was filtered off and dried, yielding 0.3 g of [2-chloro-4-(3-chlorophenyl)-6-quinazolinyl](4-fluorophenyl)-methanone (intermediate 6), mp. 138° C.

後処理

  1. temperaturecooled to room temperature
  2. customThe solvent was evaporated
  3. customThe solvent was evaporated till dryness
  4. additionpoured out into ice water
  5. extractionextracted with DCM
  6. washThe organic layer was washed with water
  7. customseparated
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent was evaporated
  11. customThe residue was crystallized from 2-propanone
  12. filtrationThe precipitate was filtered off
  13. customdried

出典と根拠

ORDレコード
ord-811dcd1b6fb74c07ae99ce1c64a9a47d
出典データセット
uspto-grants-2009_03
特許番号
US07511138B2

反応ノート

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