Dimethyl Sulfoxide → 218281-25-5

HRID 431024Notes

Reaction equation

HRID 431024 reaction equation
CS(C)=O.[CH:5]1([N:8]2[C:17]3[C:12](=[CH:13][C:14]([F:21])=[C:15](F)[C:16]=3[O:18][CH3:19])[C:11](=[O:22])[C:10]([C:23]([OH:25])=[O:24])=[CH:9]2)[CH2:7][CH2:6]1.C(OC([NH:33][C@H:34]1[C@@H:38]([CH2:39][F:40])[CH2:37][NH:36][CH2:35]1)=O)(C)(C)C>C(N(CC)CC)C>[NH2:33][C@H:34]1[C@@H:38]([CH2:39][F:40])[CH2:37][N:36]([C:15]2[C:16]([O:18][CH3:19])=[C:17]3[C:12]([C:11](=[O:22])[C:10]([C:23]([OH:25])=[O:24])=[CH:9][N:8]3[CH:5]3[CH2:6][CH2:7]3)=[CH:13][C:14]=2[F:21])[CH2:35]1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 70194651-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acidHCID 10513010HCID 10513010, compound

Product 1

HCID 9843521218281-25-5Yield 47%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a dimethyl sulfoxide (2 ml) solution of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3carboxylic acid EF2 complex (345 mg, 1.00 mmol) were added 3-(S)-tert-butoxycarbonylamino-4-(S)-fluoromethylpyrrolidine (327 mg, 1.00 mmol) and triethylamine (400 μl), subsequently carrying out 1 day of stirring at room temperature. Triethylamine was evaporated, the resulting residue was mixed with 10% citric acid aqueous solution and then the thus precipitated material was collected by filtration and washed with water. This was dissolved in 80% water-containing ethanol (50 ml), mixed with triethylamine (5 ml) and then heated overnight under reflux. The solvent was evaporated, and the thus obtained residue was mixed with concentrated hydrochloric acid and stirred at room temperature for 15 minutes. The reaction solution was washed with chloroform and then, while cooling in an ice bath, alkalified with 50% sodium hydroxide aqueous solution. This was adjusted to pH 7.4 with concentrated hydrochloric acid, and the aqueous layer was extracted with chloroform (300 ml×3). The organic layer was dried over sodium sulfate, the solvent was evaporated, and the resulting residue was isolated and purified by a preparative TLC through its development with a lower layer of chloroform:methanol:water=7:3:1 and then recrystallized from 28% aqueous ammonia-ethanol to give 185 mg (47%) of the title compound in the form of light yellow crystals.

Workup

  1. customTriethylamine was evaporated
  2. additionthe resulting residue was mixed with 10% citric acid aqueous solution
  3. filtrationthe thus precipitated material was collected by filtration
  4. washwashed with water
  5. dissolutionThis was dissolved in 80% water-
  6. additioncontaining ethanol (50 ml)
  7. additionmixed with triethylamine (5 ml)
  8. temperatureheated overnight
  9. temperatureunder reflux
  10. customThe solvent was evaporated
  11. additionthe thus obtained residue was mixed with concentrated hydrochloric acid
  12. stirringstirred at room temperature for 15 minutes
  13. washThe reaction solution was washed with chloroform
  14. temperaturewhile cooling in an ice bath
  15. extractionthe aqueous layer was extracted with chloroform (300 ml×3)
  16. dry with materialThe organic layer was dried over sodium sulfate
  17. customthe solvent was evaporated
  18. customthe resulting residue was isolated
  19. custompurified by a preparative TLC through its development with a lower layer of chloroform
  20. custommethanol:water=7:3:1 and then recrystallized from 28% aqueous ammonia-ethanol

Sources & evidence

ORD record
ord-410016ceb071492a8966e3d3d9a726d1
Source dataset
uspto-grants-2003_12
Patent number
US06656952B2

Reaction notes

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