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

HRID 580582Notes

Reaction equation

HRID 580582 reaction equation
[Cl:1][C:2]1[C:3](F)=[C:4]([F:19])[CH:5]=[C:6]2[C:11]=1[N:10]([CH:12]1[CH2:14][CH2:13]1)[CH:9]=[C:8]([C:15]([OH:17])=[O:16])[C:7]2=[O:18].C(OC([NH:28][C@H:29]1[C@@H:33]([CH3:34])[CH2:32][NH:31][CH2:30]1)=O)(C)(C)C.C1CCN2C(=NCCC2)CC1>C(#N)C>[NH2:28][C@H:29]1[C@@H:33]([CH3:34])[CH2:32][N:31]([C:3]2[C:2]([Cl:1])=[C:11]3[C:6]([C:7](=[O:18])[C:8]([C:15]([OH:17])=[O:16])=[CH:9][N:10]3[CH:12]3[CH2:14][CH2:13]3)=[CH:5][C:4]=2[F:19])[CH2:30]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 98359418-Chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acidHCID 11138119(3S,4S)-3-(Boc-amino)-4-methylpyrrolidine

Product 1

HCID 703537937-(cis-3-Amino-4-methyl-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acidYield 73.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (1.8 g), anhydrous acetonitrile (18 ml), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (reference example 3; 1.81 g) and DBU (0.90 g) was refluxed for an hour. The resulting mixture was concentrated under reduced pressure, the resulting residue was dissolved in chloroform and washed with 10% aqueous citric acid solution. The chloroform layer was further washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in hot methanol (25 ml) and, after cooling, the resulting precipitate was collected by filtration. Then this precipitate was suspended in methanol (18 ml), to this solution was added concentrated hydrochloric acid (18 ml) dropwise and stirred at room temperature for 15 minutes. The reacting mixture was neutralized with concentrated aqueous ammonia, after cooling, the resulting precipitate was collected by filtration and washed with water, methanol and ether successively to give the title compound (1.67 g) as white powder, mp 240°-243° C. (decompd.).

Workup

  1. temperaturewas refluxed for an hour
  2. concentrationThe resulting mixture was concentrated under reduced pressure
  3. dissolutionthe resulting residue was dissolved in chloroform
  4. washwashed with 10% aqueous citric acid solution
  5. washThe chloroform layer was further washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe resulting residue was dissolved in hot methanol (25 ml)
  9. temperatureafter cooling
  10. filtrationthe resulting precipitate was collected by filtration
  11. additionwas added concentrated hydrochloric acid (18 ml) dropwise
  12. temperatureafter cooling
  13. filtrationthe resulting precipitate was collected by filtration
  14. washwashed with water, methanol and ether successively

Sources & evidence

ORD record
ord-b084c2cbf8e8405e840f999a19dd6745
Source dataset
uspto-grants-1988_06
Patent number
US04753953

Reaction notes

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