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

HRID 1791827Notes

Reaction equation

HRID 1791827 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-5765a1308ef94c4a807537fe1e5994c7
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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