Potassium Carbonate → 6-Methoxy-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)-4-(quinolin-7-yloxy)quinazoline

HRID 1791552Notes

Reaction equation

HRID 1791552 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[OH:28][C:29]1[CH:38]=[C:37]2[C:32]([CH:33]=[CH:34][CH:35]=[N:36]2)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH2:18][CH2:17]1)[N:5]=[CH:4][N:3]=[C:2]2[O:28][C:29]1[CH:38]=[C:37]2[C:32]([CH:33]=[CH:34][CH:35]=[N:36]2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 220305344-Chloro-6-methoxy-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)quinazolineHCID 1354268667-Hydroxyquinoline

Product 1

HCID 98067766-Methoxy-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)-4-(quinolin-7-yloxy)quinazolineYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-chloro-6-methoxy-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)quinazoline (115 mg, 0.28 mmol) and 7-hydroxyquinoline (50 mg, 0.33 mmol) in DMF (1.5 ml) was added potassium carbonate (60 mg, 0.42 mmol). The mixture was stirred for 2 hours at 100° C. After cooling, and removal of the volatiles by evaporation, the residue was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with ethylacetate/methylene chloride/methanol (1/1/0 followed by 40/50/10 and 0/9/1). After removal of the volatiles by evaporation, the residue was triturated with pentane, filtered and dried under vacuum to give 6-methoxy-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)-4-(quinolin-7-yloxy)quinazoline (110 mg, 76%).

Workup

  1. temperatureAfter cooling
  2. customremoval of the volatiles
  3. customby evaporation
  4. customthe residue was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by column chromatography
  9. washeluting with ethylacetate/methylene chloride/methanol (1/1/0 followed by 40/50/10 and 0/9/1)
  10. customAfter removal of the volatiles
  11. customby evaporation
  12. customthe residue was triturated with pentane
  13. filtrationfiltered
  14. customdried under vacuum

Sources & evidence

ORD record
ord-e69b470660054ac7b140a6bbb2387121
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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