Sodium hydride → 4-(6-Cyanooxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline

HRID 1386343ノート

反応式

HRID 1386343 の反応式
[H-].[Na+].[C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH2:9][C:10](=[O:14])[NH:11]2)=[CH:7][CH:6]=1)#[N:4].Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1>>[C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]([C:16]3[C:25]4[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][CH2:31][N:32]5[CH2:33][CH2:34][O:35][CH2:36][CH2:37]5)=[C:23]([O:26][CH3:27])[CH:24]=4)[N:19]=[CH:18][N:17]=3)[C:10](=[O:14])[NH:11]2)=[CH:7][CH:6]=1)#[N:4]

参加物

4

反応物 3

HCID 24758Sodium hydrideHCID 27733482-Oxindole-6-carbonitrileHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

生成物 1

HCID 101952864-(6-Cyanooxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline収率 13.3%

実験手順

Sodium hydride (80 mg, 2.07 mmol) was added to a solution of 6-cyanooxindole (280 mg, 1.78 mmol), (prepared as described for the starting material in Example 57), in dry, degassed DMF (10 ml) and the suspension stirred for 15 minutes at ambient temperature. A solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (200 mg, 0.59 mmol), (prepared as described for the starting material in Example 5), in a dry, degassed mixture of DMF (2 ml) and THF (2 ml) was added dropwise and the reaction mixture was heated at 60° C. for 3 hours. The mixture was allowed to cool, the solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and the aqueous phase extracted with ethyl acetate (50 ml×3). The ethyl acetate fractions were combined, dried (MgSO4), the solvent removed by evaporation and the residue was purified by flash column chromatography eluting with methylene chloride/methanol (100/13). The purified product was triturated in boiling ether and the solid product collected by filtration to give 4-(6-cyanooxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (36 mg, 13%) as an orange solid.

後処理

  1. custom(prepared
  2. customin dry
  3. customdegassed DMF (10 ml)
  4. customdegassed
  5. additionmixture of DMF (2 ml) and THF (2 ml)
  6. additionwas added dropwise
  7. temperaturethe reaction mixture was heated at 60° C. for 3 hours
  8. temperatureto cool
  9. customthe solvents were removed by evaporation
  10. customthe residue was partitioned between ethyl acetate and water
  11. customThe organic phase was separated
  12. extractionthe aqueous phase extracted with ethyl acetate (50 ml×3)
  13. dry with materialdried (MgSO4)
  14. customthe solvent removed by evaporation
  15. customthe residue was purified by flash column chromatography
  16. washeluting with methylene chloride/methanol (100/13)
  17. customThe purified product was triturated
  18. filtrationthe solid product collected by filtration

出典と根拠

ORDレコード
ord-cade34b43cba4955b6dd3c0c12f1f42f
出典データセット
uspto-grants-2001_07
特許番号
US06265411B1

反応ノート

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