Triethylamine → 7-{3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidin-1-yl}-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 600911Notes

Reaction equation

HRID 600911 reaction equation
F[C:2]1[C:11]([O:12][CH3:13])=[C:10]2[C:5]([C:6](=[O:21])[C:7]([C:18]([OH:20])=[O:19])=[CH:8][N:9]2[C@@H:14]2[CH2:16][C@@H:15]2[F:17])=[CH:4][CH:3]=1.[C:22]([O:26][C:27]([NH:29][C:30]1([C@@H:34]2[CH2:38][CH2:37][NH:36][CH2:35]2)[CH2:33][CH2:32][CH2:31]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(N(CC)CC)C>CS(C)=O>[C:22]([O:26][C:27]([NH:29][C:30]1([C@@H:34]2[CH2:38][CH2:37][N:36]([C:2]3[C:11]([O:12][CH3:13])=[C:10]4[C:5]([C:6](=[O:21])[C:7]([C:18]([OH:20])=[O:19])=[CH:8][N:9]4[C@@H:14]4[CH2:16][C@@H:15]4[F:17])=[CH:4][CH:3]=3)[CH2:35]2)[CH2:31][CH2:32][CH2:33]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 120824067-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acidHCID 672716403-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidine

Product 1

HCID 672704287-{3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidin-1-yl}-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (290 mg, 0.98 mmol), 3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidine (283 mg, 1.18 mmol), triethylamine (0.409 ml, 2.94 mmol), and dimethyl sulfoxide (5 ml) was stirred for 112 hours while heating in an oil bath at 80° C. under an argon-replaced atmosphere. After evaporating the solvent, the residue was partitioned in chloroform (50 ml) and 10% aqueous citric acid solution (30 ml), and after separating the organic layer, the organic layer was washed with saturated saline solution (30 ml). The organic layer obtained was then dried over anhydrous sodium sulfate, and after removing the drying agent by filtration, the solvent was evaporated under a reduced pressure. The residue was subject to a silica gel chromatography and a crude 7-{3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidin-1-yl}-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid was thereby obtained from a chloroform:methanol=20:1 eluate.

Workup

  1. customAfter evaporating the solvent
  2. customthe residue was partitioned in chloroform (50 ml)
  3. custom10% aqueous citric acid solution (30 ml), and after separating the organic layer
  4. washthe organic layer was washed with saturated saline solution (30 ml)
  5. customThe organic layer obtained
  6. dry with materialwas then dried over anhydrous sodium sulfate
  7. customafter removing the drying agent
  8. filtrationby filtration
  9. customthe solvent was evaporated under a reduced pressure

Sources & evidence

ORD record
ord-72f29c1a95f1449fbd8306720b724087
Source dataset
uspto-grants-2011_03
Patent number
US07902226B2

Reaction notes

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