Dimethyl Sulfoxide → 7-[3-(R)-(1-aminocyclopropyl)pyrrolidin-1-yl]-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 600867Notes

Reaction equation

HRID 600867 reaction equation
C(OC([NH:8][C:9]1([C@@H:12]2[CH2:16][CH2:15][NH:14][CH2:13]2)[CH2:11][CH2:10]1)=O)(C)(C)C.C(N(CC)CC)C.CS(C)=O.F[C:29]1[CH:38]=[C:37]2[C:32]([C:33](=[O:46])[C:34]([C:43]([OH:45])=[O:44])=[CH:35][N:36]2[C@@H:39]2[CH2:41][C@@H:40]2[F:42])=[CH:31][CH:30]=1>O>[NH2:8][C:9]1([C@@H:12]2[CH2:16][CH2:15][N:14]([C:29]3[CH:38]=[C:37]4[C:32]([C:33](=[O:46])[C:34]([C:43]([OH:45])=[O:44])=[CH:35][N:36]4[C@@H:39]4[CH2:41][C@@H:40]4[F:42])=[CH:31][CH:30]=3)[CH2:13]2)[CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 11117758(R)-t-Butyl (1-(pyrrolidin-3-yl)cyclopropyl)carbamateHCID 672714987-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-Carboxylic Acid

Product 1

HCID 588823657-[3-(R)-(1-aminocyclopropyl)pyrrolidin-1-yl]-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 74%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

After adding 3-(R)-[1-[N-(tert-butoxycarbonyl)amino]cyclopropyl]pyrrolidine (203 mg, 817 μmol) and triethylamine (0.5 ml) to dried dimethyl sulfoxide (1 ml), 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (197 mg, 743 μmol) was added thereto and the mixture was heated reflux for 15 hours under a nitrogen atmosphere. After letting the reaction solution cool, water (30 ml) was added to the reaction solution while cooling with ice, and the precipitated crystals were filtered out and washed well with water. After adding concentrated hydrochloric acid (5 ml) to the obtained crystals while cooling with ice, stirring at the same temperature was performed for 30 minutes. 1 mol/l hydrochloric acid (10 ml) was then added to the reaction solution, and after washing the yellow acidic aqueous solution with chloroform (50 ml×2), the pH was adjusted to 12.0 with an aqueous sodium hydroxide solution. After adjusting the pH of the basic aqueous solution to 7.4 with 1 mol/l hydrochloric acid, extractions into chloroform (100 ml×3) and a 95:5 mixture of chloroform:methanol (100 ml×2) were performed. The organic layers were then combined, and after drying the organic layer over anhydrous sodium sulfate, the solvent was evapolated under a reduced pressure. The residue obtained was purified by recrystallization in ethanol and then dried under a reduced pressure. 203 mg (74%) of the title compound was thereby obtained in the form of yellow crystals.

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperaturereflux for 15 hours under a nitrogen atmosphere
  4. temperaturecool
  5. temperaturewhile cooling with ice
  6. filtrationthe precipitated crystals were filtered out
  7. washwashed well with water
  8. additionAfter adding concentrated hydrochloric acid (5 ml) to the obtained crystals
  9. temperaturewhile cooling with ice
  10. addition1 mol/l hydrochloric acid (10 ml) was then added to the reaction solution
  11. washafter washing the yellow acidic aqueous solution with chloroform (50 ml×2)
  12. extractionwith 1 mol/l hydrochloric acid, extractions into chloroform (100 ml×3)
  13. additiona 95:5 mixture of chloroform
  14. dry with materialafter drying the organic layer over anhydrous sodium sulfate
  15. customThe residue obtained
  16. customwas purified by recrystallization in ethanol
  17. customdried under a reduced pressure

Sources & evidence

ORD record
ord-3404e9b7ce0f4c24950d36a947bdbc2e
Source dataset
uspto-grants-2011_03
Patent number
US07902226B2

Reaction notes

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