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

HRID 454308노트

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HRID 454308 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[C:32]([N+:40]([O-:42])=[O:41])=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][CH:35]=[CH:34]2>CC(N(C)C)=O>[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]=[C:4]([O:30][C:31]1[C:32]([N+:40]([O-:42])=[O:41])=[C:33]3[C:37](=[CH:38][CH:39]=1)[NH:36][CH:35]=[CH:34]3)[N:3]=[CH:2]2

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 110021914-Chloro-6-methoxy-7-(3-(piperidin-1-YL)propoxy)quinazolineHCID 156921694-nitro-1H-indol-5-ol

생성물 1

HCID 220307416-Methoxy-(4-nitroindol-5-yloxy)-7-(3-piperidinopropoxy)quinazoline수율 39%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
90 °C

실험 절차

Nitrogen was bubbled through a mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (114 mg, 0.34 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (141 mg, 1.02 mmol), 5-hydroxy-4-nitroindole (60.5 mg, 0.34 mmol) and DMA (8.5 ml) for 5 minutes at ambient temperature. This mixture was then stirred at 90° C. for 4 hours under an atmosphere of nitrogen and allowed to cool to ambient temperature. The reaction mixture was filtered and the filtrate evaporated in vacuo. The residue was purified by silica column chromatography using gradient elution with dichloromethane/methanol (100/0 to 95/5) followed by dichloromethane/methanolic ammonia (7M) (95/5) to give a partially purified oil. This oil was further purified by silica column chromatography, gradient elution with ethyl acetate/methanolic ammonia (95/5 to 80/20) to give 6-methoxy-(4-nitroindol-5-yloxy)-7-(3-piperidinopropoxy)quinazoline (63 mg, 39%).

후처리

  1. custom(prepared
  2. customfor 5 minutes
  3. customat ambient temperature
  4. temperatureto cool to ambient temperature
  5. filtrationThe reaction mixture was filtered
  6. customthe filtrate evaporated in vacuo
  7. customThe residue was purified by silica column chromatography
  8. washelution with dichloromethane/methanol (100/0 to 95/5)
  9. customto give a partially purified oil
  10. customThis oil was further purified by silica column chromatography, gradient elution with ethyl acetate/methanolic ammonia (95/5 to 80/20)

출처 및 근거

ORD 기록
ord-2909bf485a8d469ea2de8b78ea70896e
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08492560B2

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