N-Methylpiperidine → 7-[3-(r)-(1-Aminocyclopropyl)pyrrolidin-1-yl]-1-[2-(s)-fluoro-1-(r)-cyclopropyl]-5-hydroxy-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 600909Notes

Reaction equation

HRID 600909 reaction equation
F[C:2]1[C:11]([CH3:12])=[C:10]2[C:5]([C:6](=[O:20])[C:7]([C:17]([OH:19])=[O:18])=[CH:8][N:9]2[C@@H:13]2[CH2:15][C@@H:14]2[F:16])=[C:4]([OH:21])[CH:3]=1.C(OC([NH:29][C:30]1([C@@H:33]2[CH2:37][CH2:36][NH:35][CH2:34]2)[CH2:32][CH2:31]1)=O)(C)(C)C.CN1CCCCC1>CS(C)=O>[NH2:29][C:30]1([C@@H:33]2[CH2:37][CH2:36][N:35]([C:2]3[C:11]([CH3:12])=[C:10]4[C:5]([C:6](=[O:20])[C:7]([C:17]([OH:19])=[O:18])=[CH:8][N:9]4[C@@H:13]4[CH2:15][C@@H:14]4[F:16])=[C:4]([OH:21])[CH:3]=3)[CH2:34]2)[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 12291N-MethylpiperidineHCID 11117758(R)-t-Butyl (1-(pyrrolidin-3-yl)cyclopropyl)carbamateHCID 672715427-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-hydroxy-8-methyl-1,4-dihydro-4-oxoquinoline-3-Carboxylic Acid

Product 1

HCID 672719247-[3-(r)-(1-Aminocyclopropyl)pyrrolidin-1-yl]-1-[2-(s)-fluoro-1-(r)-cyclopropyl]-5-hydroxy-8-methyl-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]-5-hydroxy-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (205 mg, 0.694 mmol), 3-(R)-[1-(tert-butoxycarbonylamino)cyclopropyl]pyrrolidine (314 mg, 1.388 mmol), N-methyl piperidine (0.243 ml, 1.388 mmol), and dimethyl sulfoxide (1.5 ml) was stirred for 66 hours while heating in an oil bath at 80° C. under a nitrogen-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 aqueous layer was further subject to extraction into chloroform (30 ml). The combined organic layer was then dried over anhydrous sodium sulfate, and after removing the drying agent by filtration, the solvent was evaporated under a reduced pressure to thereby obtain a crude 7-{3-(R)-[1-(tert-butoxycarbonylamino)cyclopropyl]pyrrolidin-1-yl}-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-hydroxy-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid.

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. extractionthe aqueous layer was further subject to extraction into chloroform (30 ml)
  5. dry with materialThe combined organic layer was then dried over anhydrous sodium sulfate
  6. customafter removing the drying agent
  7. filtrationby filtration
  8. customthe solvent was evaporated under a reduced pressure

Sources & evidence

ORD record
ord-706bfe948b1e4e01ab4381348b6a46f0
Source dataset
uspto-grants-2011_03
Patent number
US07902226B2

Reaction notes

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