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

HRID 454146Notes

Reaction equation

HRID 454146 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[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
95 °C

Procedure

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%).

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 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

Sources & evidence

ORD record
ord-93b9de381ed74f459a52faa6610927c3
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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