Methanesulfonic Acid → 3-(7-Hydroxy-6-methoxy-quinolin-4-yloxy)-2-methyl-[1,6]naphthyridine

HRID 229009Notes

Reaction equation

HRID 229009 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[C:21]([CH3:30])=[N:22][C:23]4[C:28]([CH:29]=3)=[CH:27][N:26]=[CH:25][CH:24]=4)=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:31][CH3:32])C1C=CC=CC=1.CS(O)(=O)=O>FC(F)(F)C(O)=O>[OH:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[C:21]([CH3:30])=[N:22][C:23]4[C:28]([CH:29]=3)=[CH:27][N:26]=[CH:25][CH:24]=4)=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:31][CH3:32]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 230784443-(7-Benzyloxy-6-methoxy-quinolin-4-yloxy)-2-methyl-[1,6]naphthyridine2×

Product 1

HCID 1358548323-(7-Hydroxy-6-methoxy-quinolin-4-yloxy)-2-methyl-[1,6]naphthyridineYield 98.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
70 °C

Procedure

3-(7-Benzyloxy-6-methoxy-quinolin-4-yloxy)-2-methyl-[1,6]naphthyridine (compound 406) (590 mg) was dissolved in trifluoroacetic acid (6 ml) to preapre a solution. Methanesulfonic acid (0.6 ml) was added to the solution, and the mixture was stirred at 70° C. for one hr. The reaction solution was cooled to room temperature, and the solvent was removed by distillation under the reduced pressure. An aqueous sodium hydrogencarbonate solution was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give 3-(7-hydroxy-6-methoxy-quinolin-4-yloxy)-2-methyl-[1,6]naphthyridine (456 mg, yield 98%).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. customthe solvent was removed by distillation under the reduced pressure
  3. additionAn aqueous sodium hydrogencarbonate solution was then added to the residue
  4. extractionthe mixture was extracted with chloroform
  5. washThe chloroform layer was washed with saturated brine
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. customThe solvent was removed by distillation under the reduced pressure
  8. customthe residue was purified by thin layer chromatography

Sources & evidence

ORD record
ord-2eea6e39fec943f6b663b03e8bdd3d27
Source dataset
uspto-grants-2009_07
Patent number
US07560558B2

Reaction notes

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