Potassium Carbonate → 6-Methoxy-7-(3-piperidinopropoxy)-4(6-trifluoromethylindol-5-yloxy)quinazoline

HRID 1791671노트

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HRID 1791671 반응식
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[OH:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][C:39]=1[C:40]([F:43])([F:42])[F:41])[NH:36][CH:35]=[CH:34]2.CC(N(C)C)=O>ClCCl>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)[N:5]=[CH:4][N:3]=[C:2]2[O:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][C:39]=1[C:40]([F:43])([F:41])[F:42])[NH:36][CH:35]=[CH:34]2

참가 물질

6

반응물 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 110021914-Chloro-6-methoxy-7-(3-(piperidin-1-YL)propoxy)quinazolineHCID 220307041H-Indol-5-ol, 6-(trifluoromethyl)-

생성물 1

HCID 220308006-Methoxy-7-(3-piperidinopropoxy)-4(6-trifluoromethylindol-5-yloxy)quinazoline수율 25%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
95 °C

실험 절차

A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (168 mg, 0.5 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (276 mg, 2.0 mmol) and 5-hydroxy-6-trifluoromethylindole (110 mg, 0.55 mmol) and DMA (4.0 ml) were stirred at 95° C. for 1.5 hours and allowed to cool to ambient temperature. The reaction mixture was filtered and the filtrate evaporated under vacuum. The residue was purified by silica column chromatography eluting with dichloromethane/methanol/0.880 aqueous ammonia (89/10/1) to give a partially purified oil. This oil was further purified by high performance column chromatography on octadecylsilane reverse phase silica eluting with acetonitrile/water/trifluoroacetic acid (60/39.8/0.2) to give an oil which was dissolved in dichloromethane and washed with saturated aqueous sodium hydrogen carbonate solution. The dichloromethane layer was evaporated to give 6-methoxy-7-(3-piperidinopropoxy)-4(6-trifluoromethylindol-5-yloxy)quinazoline (62 mg, 25%).

후처리

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. filtrationThe reaction mixture was filtered
  4. customthe filtrate evaporated under vacuum
  5. customThe residue was purified by silica column chromatography
  6. washeluting with dichloromethane/methanol/0.880 aqueous ammonia (89/10/1)
  7. customto give a partially purified oil
  8. customThis oil was further purified by high performance column chromatography on octadecylsilane reverse phase silica eluting with acetonitrile/water/trifluoroacetic acid (60/39.8/0.2)
  9. customto give an oil which
  10. washwashed with saturated aqueous sodium hydrogen carbonate solution
  11. customThe dichloromethane layer was evaporated

출처 및 근거

ORD 기록
ord-9ffd160700234287a5acf4978eea8324
출처 데이터셋
uspto-grants-2006_07
특허 번호
US07074800B1

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