Dimethyl Sulfoxide → 8-Amino-10-(1-amino-3-azabicyclo[3,1.0]hexan-3-yl)-9-fluoro-2,3-dihydro-3-(S)-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylic acid

HRID 635798Notes

Reaction equation

HRID 635798 reaction equation
CS(C)=O.[NH2:5][C:6]1[C:19]2[C:18](=[O:20])[C:17]([C:21]([OH:23])=[O:22])=[CH:16][N:11]3[C@@H:12]([CH3:15])[CH2:13][O:14][C:9]([C:10]=23)=[C:8](F)[C:7]=1[F:25].C(OC([NH:33][C:34]12[CH2:39][CH:38]1[CH2:37][NH:36][CH2:35]2)=O)(C)(C)C>C(N(CC)CC)C>[NH2:5][C:6]1[C:19]2[C:18](=[O:20])[C:17]([C:21]([OH:23])=[O:22])=[CH:16][N:11]3[C@@H:12]([CH3:15])[CH2:13][O:14][C:9]([C:10]=23)=[C:8]([N:36]2[CH2:37][CH:38]3[C:34]([NH2:33])([CH2:39]3)[CH2:35]2)[C:7]=1[F:25]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 21256582Carbamic acid, 3-azabicyclo[3.1.0]hex-1-YL-, 1,1-dimethylethyl esterHCID 21971273(S)-8-Amino-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid

Product 1

HCID 99075868-Amino-10-(1-amino-3-azabicyclo[3,1.0]hexan-3-yl)-9-fluoro-2,3-dihydro-3-(S)-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylic acidYield 63%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

To a dimethyl sulfoxide (5 ml) solution of 8-amino-9,10-difluoro-2,3-dihydro-3-(S)-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (200 mg, 0.68 mmol) were added 1-tert-butoxycarbonylamino-3-azabicyclo[3.1.0]hexane (Fr. 1; 270 mg, 1.36 mmol) and triethylamine (1 ml), and the mixture was heated at 100° C. for 24 hours. After evaporation of the solvent under a reduced pressure, the thus obtained residue was mixed with chloroform (50 ml), the resulting solution was washed with 10% citric acid (20 ml×2) and dried over sodium sulfate, and then the solvent was evaporated under a reduced pressure. The thus obtained residue was mixed with concentrated hydrochloric acid (5 ml) and stirred at room temperature for 5 minutes, and the mixture was washed with chloroform (30 ml×3), alkalified by adding 20% sodium hydroxide aqueous solution, then, adjusted to pH 7.2 with concentrated hydrochloric acid and extracted with chloroform (50 ml×3). The extract was dried over sodium sulfate, and the solvent was evaporated under a reduced pressure to yield 201 mg of the crude title compound. By recrystallizing this from 28% ammonia aqueous solution-ethanol, 160 mg (63%) of the title compound was obtained.

Workup

  1. customAfter evaporation of the solvent under a reduced pressure
  2. additionthe thus obtained residue was mixed with chloroform (50 ml)
  3. washthe resulting solution was washed with 10% citric acid (20 ml×2)
  4. dry with materialdried over sodium sulfate
  5. customthe solvent was evaporated under a reduced pressure
  6. additionThe thus obtained residue was mixed with concentrated hydrochloric acid (5 ml)
  7. washthe mixture was washed with chloroform (30 ml×3)
  8. additionby adding 20% sodium hydroxide aqueous solution
  9. extractionextracted with chloroform (50 ml×3)
  10. dry with materialThe extract was dried over sodium sulfate
  11. customthe solvent was evaporated under a reduced pressure
  12. customto yield 201 mg of the crude title compound
  13. customBy recrystallizing this from 28% ammonia aqueous solution-ethanol

Sources & evidence

ORD record
ord-dc3250f7262641bdb0c05996100bc5fc
Source dataset
uspto-grants-2001_02
Patent number
US06191129B1

Reaction notes

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