1,8-Diazabicyclo(5.4.0)undec-7-ene → 7-(cis-3-Amino-4-methyl-1-pyrrolidinyl)-1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

HRID 580588Notes

Reaction equation

HRID 580588 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2].C(OC([NH:27][C@H:28]1[C@@H:32]([CH3:33])[CH2:31][NH:30][CH2:29]1)=O)(C)(C)C.C1CCN2C(=NCCC2)CC1>C(#N)C>[NH2:27][C@H:28]1[C@@H:32]([CH3:33])[CH2:31][N:30]([C:10]2[C:11]([F:13])=[C:12]3[C:7]([C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4][N:3]3[CH2:1][CH3:2])=[CH:8][C:9]=2[F:15])[CH2:29]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 98351791-Ethyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acidHCID 11138119(3S,4S)-3-(Boc-amino)-4-methylpyrrolidine

Product 1

HCID 704198657-(cis-3-Amino-4-methyl-1-pyrrolidinyl)-1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acidYield 31.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (1.0 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.89 g), DBU (0.62 g) and anhydrous acetonitrile (30 ml) was refluxed for 2 hours and then concentrated. The resulting residue was dissolved in chloroform (50 ml), washed with 10% aqueous citric acid solution and water successively, dried over anhydrous sodium sulfate and concentrated. To the resulting residue was added hot methanol to crystallize and then cooled. The resulting precipitate was collected by filtration, added to the mixture of concentrated hydrochloric acid-methanol (1:1, 18 ml) and stirred at room temperature for an hour. The reacting mixture was neutralized with concentrated aqueous ammonia and the resulting precipitate was collected by filtration, washed with ice-water sufficiently and recrystallized from dichloromethane-methanol (1:1) to give the title compound (0.41 g) as colorless prisms, mp 232°-234° C. (decompd.).

Workup

  1. temperaturewas refluxed for 2 hours
  2. concentrationconcentrated
  3. dissolutionThe resulting residue was dissolved in chloroform (50 ml)
  4. washwashed with 10% aqueous citric acid solution and water successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. additionTo the resulting residue was added hot methanol
  8. customto crystallize
  9. temperaturecooled
  10. filtrationThe resulting precipitate was collected by filtration
  11. additionadded to the mixture of concentrated hydrochloric acid-methanol (1:1, 18 ml)
  12. filtrationthe resulting precipitate was collected by filtration
  13. washwashed with ice-water sufficiently
  14. customrecrystallized from dichloromethane-methanol (1:1)

Sources & evidence

ORD record
ord-e83cd15b9ef14c4a8dbcdbc103c64724
Source dataset
uspto-grants-1988_06
Patent number
US04753953

Reaction notes

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