(S)-tert-Butyl 5-azaspiro[2.4]heptan-7-ylcarbamate → 7-[7-(S)-Amino-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

HRID 1939273Notes

Reaction equation

HRID 1939273 reaction equation
[F:1][C:2]1[C:3]([CH3:21])=[C:4]2[C:9](=[CH:10][C:11]=1F)[N:8]([C@@H:13]1[CH2:15][C@@H:14]1[F:16])[CH:7]=[C:6]([C:17]([OH:19])=[O:18])[C:5]2=[O:20].C(OC([NH:29][C@H:30]1[C:34]2([CH2:36][CH2:35]2)[CH2:33][NH:32][CH2:31]1)=O)(C)(C)C>CS(C)=O>[NH2:29][C@H:30]1[C:34]2([CH2:36][CH2:35]2)[CH2:33][N:32]([C:11]2[CH:10]=[C:9]3[C:4]([C:5](=[O:20])[C:6]([C:17]([OH:19])=[O:18])=[CH:7][N:8]3[C@@H:13]3[CH2:15][C@@H:14]3[F:16])=[C:3]([CH3:21])[C:2]=2[F:1])[CH2:31]1

Participants

4

Reactant 2

HCID 10353141(S)-tert-Butyl 5-azaspiro[2.4]heptan-7-ylcarbamateHCID 228799656,7-Difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

Product 1

HCID 228799637-[7-(S)-Amino-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic AcidYield 46.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 200 mg of 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 287 mg of 7-(S)-t-butoxycarbonylamino-5-azaspiro[2.4]heptane, and 5 ml of anhydrous dimethyl sulfoxide was heated at 100° C. for 30 minutes with stirring. After allowing to cool, the reaction mixture was concentrated under reduced pressure, and water was added to the residue. The precipitated yellow crystals were collected by filtration and added to 5 ml of trifluoroacetic acid while stirring and cooling with ice, followed by stirring at room temperature for 30 minutes. The reaction mixture was further worked up in the same manner as in Example 7. Recrystallization of the crude crystal from ethanol gave 122 mg of the titled compound as a pale yellow powder.

Workup

  1. temperatureto cool
  2. concentrationthe reaction mixture was concentrated under reduced pressure, and water
  3. additionwas added to the residue
  4. filtrationThe precipitated yellow crystals were collected by filtration
  5. additionadded to 5 ml of trifluoroacetic acid
  6. stirringwhile stirring
  7. temperaturecooling with ice
  8. stirringby stirring at room temperature for 30 minutes
  9. customRecrystallization of the crude crystal from ethanol

Sources & evidence

ORD record
ord-ade5edcba9304a37ad800bcd93be1e42
Source dataset
uspto-grants-1997_12
Patent number
US05696132

Reaction notes

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