1,8-Diazabicyclo(5.4.0)undec-7-ene → 1-Cyclopropyl-7-(3-amino-1-pyrrolidinyl)-6-fluoro-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 330086Notes

Reaction equation

HRID 330086 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[CH3:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.C(OC([NH:28][CH:29]1[CH2:33][CH2:32][NH:31][CH2:30]1)=O)(C)(C)C.C1CCN2C(=NCCC2)CC1>C(#N)C>[NH2:28][CH:29]1[CH2:33][CH2:32][N:31]([C:11]2[C:12]([CH3:14])=[C:13]3[C:8]([C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5][N:4]3[CH:1]3[CH2:3][CH2:2]3)=[CH:9][C:10]=2[F:16])[CH2:30]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 140525751-Cyclopropyl-6,7-difluoro-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

Product 1

HCID 140525771-Cyclopropyl-7-(3-amino-1-pyrrolidinyl)-6-fluoro-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 12.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylic acid (200 mg), 3-t-butoxycarbonylaminopyrrolidine (200 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (110 mg, DBU) and anhydrous acetonitrile (2 ml) was refluxed for 18 hours. The reacting mixture was concentrated under reduced pressure. The resulting residue was dissolved in chloroform (20 ml), washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution successively, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To the solution of the resulting residue in methanol (2 ml) was added concentrated hydrochloric acid (2 ml) and stirred at room temperature for 15 minutes. After the reacting mixture was neutralized with concentrated aqueous ammonia, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography eluting chloroform-methanol-concentrated aqueous ammonia (10:10:3) and recrystallized from dichloromethane-methanol further to give the title compound (30 mg) as yellow powder, mp 187°-190° C.

Workup

  1. temperaturewas refluxed for 18 hours
  2. concentrationThe reacting mixture was concentrated under reduced pressure
  3. dissolutionThe resulting residue was dissolved in chloroform (20 ml)
  4. washwashed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionTo the solution of the resulting residue in methanol (2 ml) was added concentrated hydrochloric acid (2 ml)
  8. concentrationthe mixture was concentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel chromatography
  10. washeluting chloroform-methanol-concentrated aqueous ammonia (10:10:3)
  11. customrecrystallized from dichloromethane-methanol further

Sources & evidence

ORD record
ord-856e1ce0652b4b4fb898396fed8f2c8c
Source dataset
uspto-grants-1990_01
Patent number
US04894458

Reaction notes

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