Potassium Carbonate → 4-(4-Bromoindol-5-yloxy)-6-methoxy-7-(3-piperidinopropoxy)quinazoline

HRID 454283Notes

Reaction equation

HRID 454283 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+].[Br:30][C:31]1[C:39]([OH:40])=[CH:38][CH:37]=[C:36]2[C:32]=1[CH:33]=[CH:34][NH:35]2>CC(N(C)C)=O>[Br:30][C:31]1[C:39]([O:40][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:38][CH:37]=[C:36]2[C:32]=1[CH:33]=[CH:34][NH:35]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 110021914-Chloro-6-methoxy-7-(3-(piperidin-1-YL)propoxy)quinazolineHCID 220305854-bromo-1H-Indol-5-ol

Product 1

HCID 220307204-(4-Bromoindol-5-yloxy)-6-methoxy-7-(3-piperidinopropoxy)quinazolineYield 44.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (380 mg, 1.13 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (469 mg, 3.4 mmol), 4-bromo-5-hydroxyindole (240 mg, 1.13 mmol) and DMA (4.0 ml) were stirred at 90° C. for 3 hours and allowed to cool to ambient temperature. The reaction mixture was filtered and the filtrate evaporated under vacuum. The residue was purified by column chromatography eluting with dichloromethane/methanolic ammonia (7M) (95/5) to give an oil. This oil was further purified by column chromatography eluting with dichloromethane/methanol (60/40) to give 4-(4-bromoindol-5-yloxy)-6-methoxy-7-(3-piperidinopropoxy)quinazoline (256 mg, 44%).

Workup

  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 column chromatography
  6. washeluting with dichloromethane/methanolic ammonia (7M) (95/5)
  7. customto give an oil
  8. customThis oil was further purified by column chromatography
  9. washeluting with dichloromethane/methanol (60/40)

Sources & evidence

ORD record
ord-3a6f2d35660c4a7f8584469bd77e6dc1
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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