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Chloroacetyl chloride → 7-{[1-(chloroacetyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline

HRID 1668676
ノート
印刷プレビュー

反応式

HRID 1668676 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][CH:26]=[C:25]2[CH3:31].CCN(C(C)C)C(C)C.[Cl:41][CH2:42][C:43](Cl)=[O:44]>ClCCl.CO>[Cl:41][CH2:42][C:43]([N:18]1[CH2:19][CH2:20][CH:15]([CH2:14][O:13][C:12]2[CH:11]=[C:10]3[C:5]([C:6]([O:21][C:22]4[CH:23]=[C:24]5[C:28](=[CH:29][CH:30]=4)[NH:27][CH:26]=[C:25]5[CH3:31])=[N:7][CH:8]=[N:9]3)=[CH:4][C:3]=2[O:2][CH3:1])[CH2:16][CH2:17]1)=[O:44]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 220307946-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline

生成物 1

HCID 596829177-{[1-(chloroacetyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline

試薬・触媒・溶媒 2

HCID 887Methanol溶媒
HCID 6344
Dichloromethane
溶媒

実験手順

6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline (0.4 g), prepared as described for the starting material in Example 1, was dissolved in dichloromethane (15 ml). PS-DIEA resin (0.6 g; 4 mmol/g) was added followed by chloroacetyl chloride (0.091 ml). The reaction mixture was stirred at ambient temperature for 3 hours then diluted with methanol and the resin removed by filtration. The solvent was evaporated under vacuum and the residue was purified by column chromatography on silica using increasingly polar solvent mixtures, starting with dichloromethane and ending with dichloromethane/methanol (92/8). Removal of the solvents by evaporation gave 7-{[1-(chloroacetyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline (0.237 g) as a solid foam.

後処理

  1. customthe resin removed by filtration
  2. customThe solvent was evaporated under vacuum
  3. customthe residue was purified by column chromatography on silica using
  4. temperatureincreasingly polar solvent mixtures
  5. customRemoval of the solvents
  6. customby evaporation

出典と根拠

ORDレコード
ord-db0f2c738e5b4f799a85080ce74b3e67
出典データセット
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07989460B2

反応ノート

読み込み中…

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