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

Temperatur

100 °C

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.

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

ORD-Eintrag

ord-dc3250f7262641bdb0c05996100bc5fc

Quelldatensatz

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06191129B1