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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
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HRID 1668676 반응식
[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]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매
HCID 6344
Dichloromethane
용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-db0f2c738e5b4f799a85080ce74b3e67
출처 데이터셋
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07989460B2

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