Acetonitrile → 5-Amino-7-(3-(R)-[1-amino-1-(3-pyridyl)methyl]-1-pyrrolidinyl]-6,8-difluoro-1-[(1R, 2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 1883969ノート

反応式

HRID 1883969 の反応式
C(OC([NH:8][CH:9]([C@@H:16]1[CH2:20][CH2:19][NH:18][CH2:17]1)[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=O)(C)(C)C.C(#N)C.[NH2:24][C:25]1[C:34]([F:35])=[C:33](F)[C:32]([F:37])=[C:31]2[C:26]=1[C:27](=[O:45])[C:28]([C:42]([OH:44])=[O:43])=[CH:29][N:30]2[C@@H:38]1[CH2:40][C@@H:39]1[F:41]>C(N(CC)CC)C>[NH2:24][C:25]1[C:34]([F:35])=[C:33]([N:18]2[CH2:19][CH2:20][C@@H:16]([CH:9]([NH2:8])[C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)[CH2:17]2)[C:32]([F:37])=[C:31]2[C:26]=1[C:27](=[O:45])[C:28]([C:42]([OH:44])=[O:43])=[CH:29][N:30]2[C@@H:38]1[CH2:40][C@@H:39]1[F:41]

参加物

5

反応物 3

HCID 6342AcetonitrileHCID 155235655-amino-6,7,8-trifluoro-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acidHCID 207414023-(R)-[1-Tert-butoxycarbonylamino-1-(3-pyridyl)methyl]pyrrolidine

生成物 1

HCID 184394105-Amino-7-(3-(R)-[1-amino-1-(3-pyridyl)methyl]-1-pyrrolidinyl]-6,8-difluoro-1-[(1R, 2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid収率 32.8%

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

実験手順

3-(R)-[1Tert-butoxycarbonylamino-1-(3-pyridyl)methyl)pyrrolidine [F2] (0.461 mmol) was added to an acetonitrile suspension (5 ml) of 5-amino-6,7,8-trifluoro-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (156 mg, 0.493 mmol) and the mixture was heated under reflux for 19 hours in the presence of triethylamine (0.5 ml). After cooling, the solvent of the reaction solution was evaporated under a reduced pressure. The resulting residue use dissolved in chloroform (50 ml) this was washed with 10% citric acid (40 ml) and saturated brine (40 ml) and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was mixed with concentrated hydrochloric acid (5 ml) under ice-cooling, further mixed with 1 mol/l hydrochloric acid aqueous solution (5 ml) at room temperature and then washed with chloroform (50 ml×5). This hydrochloric acid aqueous solution was adjusted to an alkaline liquid property by adding 10 mol/l sodium hydroxide aqueous solution, further adjusted to a liquid property of pH 7.4 by adding concentrated hydrochloric acid and 1 mol/l hydrochloric acid and then extracted with chloroform (150 ml×3). The resulting organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under a reduced pressure to obtain the crude title compound as light yellow crystals. This was purified by recrystallizing from ethanol to obtain 71.5 mg (32%) of the title compound.

後処理

  1. temperaturethe mixture was heated
  2. temperatureAfter cooling
  3. customthe solvent of the reaction solution was evaporated under a reduced pressure
  4. dissolutionThe resulting residue use dissolved in chloroform (50 ml)
  5. washthis was washed with 10% citric acid (40 ml) and saturated brine (40 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent was evaporated under a reduced pressure
  8. additionThe resulting residue was mixed with concentrated hydrochloric acid (5 ml) under ice-
  9. temperaturecooling
  10. additionfurther mixed with 1 mol/l hydrochloric acid aqueous solution (5 ml) at room temperature
  11. washwashed with chloroform (50 ml×5)
  12. additionby adding 10 mol/l sodium hydroxide aqueous solution
  13. additionby adding concentrated hydrochloric acid and 1 mol/l hydrochloric acid
  14. extractionextracted with chloroform (150 ml×3)
  15. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  16. customthe solvent was evaporated under a reduced pressure
  17. customto obtain the crude title compound as light yellow crystals
  18. customThis was purified
  19. customby recrystallizing from ethanol

出典と根拠

ORDレコード
ord-3840c96198914f13b15739f2fc406f12
出典データセット
uspto-grants-2004_07
特許番号
US06762181B1

反応ノート

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