Triethylamine → 5-Amino-7-[3-(1-aminocyclobutyl)-1-pyrrolidinyl]-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 1458012Notes

Reaction equation

HRID 1458012 reaction equation
C(OC([NH:8][C:9]1([CH:12]2[CH2:16][CH2:15][NH:14][CH2:13]2)[CH2:11][CH2:10]1)=O)(C)(C)C.[NH2:17][C:18]1[C:27]([F:28])=[C:26](F)[C:25]([F:30])=[C:24]2[C:19]=1[C:20](=[O:38])[C:21]([C:35]([OH:37])=[O:36])=[CH:22][N:23]2[C@@H:31]1[CH2:33][C@@H:32]1[F:34].[CH2:39](N(CC)CC)C>C(#N)C>[NH2:17][C:18]1[C:27]([F:28])=[C:26]([N:14]2[CH2:15][CH2:16][CH:12]([C:9]3([NH2:8])[CH2:11][CH2:10][CH2:39]3)[CH2:13]2)[C:25]([F:30])=[C:24]2[C:19]=1[C:20](=[O:38])[C:21]([C:35]([OH:37])=[O:36])=[CH:22][N:23]2[C@@H:31]1[CH2:33][C@@H:32]1[F:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 155235655-amino-6,7,8-trifluoro-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acidHCID 221005681-(Boc-amino)-(pyrrolidin-3-YL)-cyclopropane

Product 1

HCID 691379145-Amino-7-[3-(1-aminocyclobutyl)-1-pyrrolidinyl]-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 37%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 242 mg (1.00 mmol) portion of 3-(1-tert-butoxycarbonylaminocyclopropyl)pyrrolidine (fr.2) was suspended in 10.0 ml of acetonitrile to which was subsequently added 212 mg (0.67 mmol) of 5-amino-6,7,8-trifluoro-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 1.40 ml (6.70 mmol) of triethylamine, followed by overnight heating under reflux. After evaporation of the solvent, the resulting residue was mixed with chloroform, washed with water, 10% citric acid aqueous solution and saturated brine in that order, and then dried over anhydrous sodium sulfate, followed by evaporation of the solvent. Thereto was added 2 ml of concentrated hydrochloric acid, followed by 2 hours of stirring at room temperature. The reaction solution was mixed with 10 ml of water, washed with chloroform and then neutralized with sodium hydroxide aqueous solution. This was extracted with chloroform and dried over sodium sulfate, and then the solvent was evaporated. Thereafter, the resulting residue was recrystallized from ethanol-diisopropyl ether to yield 292 mg (37%) of the title compound as a yellow solid.

Workup

  1. temperatureheating
  2. temperatureunder reflux
  3. customAfter evaporation of the solvent
  4. additionthe resulting residue was mixed with chloroform
  5. washwashed with water, 10% citric acid aqueous solution and saturated brine in that order
  6. dry with materialdried over anhydrous sodium sulfate
  7. customfollowed by evaporation of the solvent
  8. additionThereto was added 2 ml of concentrated hydrochloric acid
  9. waitfollowed by 2 hours
  10. additionThe reaction solution was mixed with 10 ml of water
  11. washwashed with chloroform
  12. extractionThis was extracted with chloroform
  13. dry with materialdried over sodium sulfate
  14. customthe solvent was evaporated
  15. customThereafter, the resulting residue was recrystallized from ethanol-diisopropyl ether

Sources & evidence

ORD record
ord-15ad1bafd0eb4e6ba048443996007d72
Source dataset
uspto-grants-1998_12
Patent number
US05849757

Reaction notes

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