Potassium Carbonate → 6-Methoxy-7-(2-morpholinoethoxy)-4-(quinolin-7-yloxy)quinazoline

HRID 454195Notes

Reaction equation

HRID 454195 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:22]=[C:21]4[C:16]([CH:17]=[CH:18][CH:19]=[N:20]4)=[CH:15][CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].O[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)[N:9]=[CH:8][N:7]=[C:6]2[O:12][C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[N:20]2)=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 611632-MorpholinoethanolHCID 135763121HCID 135763121, compound

Product 1

HCID 220307656-Methoxy-7-(2-morpholinoethoxy)-4-(quinolin-7-yloxy)quinazolineYield 71.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 7-hydroxy-6-methoxy-4-(quinolin-7-yloxy)quinazoline (450 mg, 1.40 mmol), (prepared as described in Example 197), in DMF (50 ml) was added anhydrous potassium carbonate (773 mg, 5.60 mmol) and 4-(2-hydroxyethyl)morpholine (335 mg, 1.80 mmol), and the reaction heated under reflux for 2 hours. The DMF was evaporated in vacuo, and the residue partitioned between dichloromethane and 1N aqueous sodium hydroxide. The mixture was extracted with dichloromethane (3×200 ml), dried (MgSO4) and concentrated in vacuo. The crude product was triturated with hexane/ether to afford a solid which was filtered and dried under suction to give 6-methoxy-7-(2-morpholinoethoxy)-4-(quinolin-7-yloxy)quinazoline (430 mg, 1.00 mmol, 71%) as a light brown solid.

Workup

  1. temperaturethe reaction heated
  2. temperatureunder reflux for 2 hours
  3. customThe DMF was evaporated in vacuo
  4. customthe residue partitioned between dichloromethane and 1N aqueous sodium hydroxide
  5. extractionThe mixture was extracted with dichloromethane (3×200 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was triturated with hexane/ether
  9. customto afford a solid which
  10. filtrationwas filtered
  11. customdried under suction

Sources & evidence

ORD record
ord-f9760a15792e4c5a974c0588e85fe15b
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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