Triethylamine → 5-Amino-7-[1-amino-5-azaspiro[2.4]heptan-5-yl]-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic Acid

HRID 992440노트

반응식

HRID 992440 반응식
C(O[C:9]([N:11]1[CH2:25][CH2:24][C:13]2([CH:15]([NH:16]C(OC(C)(C)C)=O)[CH2:14]2)[CH2:12]1)=O)C1C=CC=CC=1.[NH2:26][C:27]1[C:36]([F:37])=C(F)[C:34]([F:39])=[C:33]2[C:28]=1[C:29](=[O:47])[C:30]([C:44]([OH:46])=[O:45])=[CH:31][N:32]2[C@@H:40]1[CH2:42][C@@H:41]1[F:43].C(N(CC)CC)C>C(O)C.[C].[Pd]>[NH2:26][C:27]1[C:36]([F:37])=[C:9]([N:11]2[CH2:25][CH2:24][C:13]3([CH:15]([NH2:16])[CH2:14]3)[CH2:12]2)[C:34]([F:39])=[C:33]2[C:28]=1[C:29](=[O:47])[C:30]([C:44]([OH:46])=[O:45])=[CH:31][N:32]2[C@@H:40]1[CH2:42][C@@H:41]1[F:43]

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 155235655-amino-6,7,8-trifluoro-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acidHCID 184122455-Benzyloxycarbonyl-1-tert-butoxycarbonylamino-5-azaspiro[2.4]heptane

생성물 1

HCID 228883405-Amino-7-[1-amino-5-azaspiro[2.4]heptan-5-yl]-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic Acid수율 78%

시약·촉매·용매 2

HCID 178418390HCID 178418390, 화합물촉매2회HCID 702Ethanol용매

실험 절차

A 346 mg (1.00 mmol) portion of 5-benzyloxycarbonyl-1-tert-butoxycarbonylamino-5-azaspiro[2.4]heptane (1-b) was dissolved in 30 ml of ethanol, and the solution was mixed with 350 mg of 10% palladium-carbon and subjected to 4 hours of hydrogenation under atmospheric pressure. After completion of the reaction, 10% palladium-carbon was removed by filtration and ethanol was evaporated. The thus obtained residue was suspended in 10 ml of acetonitrile, and the suspension was mixed with 210 mg (0.67 mmol) of 5-amino-6,7,8-trifluoro-1-[(1R,2S)-2-fluorocyclopropyl]1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 0.93 ml (6.67 mmol) of triethylamine, and heated under reflux for 18 hours. After evaporation of the solvent, the thus obtained residue was mixed with chloroform, washed with water, 10% citric acid aqueous solution and saturated brine in that order, and then dried over anhydrous sodium sulfate, subsequently evaporating the solvent. The thus obtained tert-butylcarbamate compound was mixed with 5 ml of concentrated hydrochloric acid, stirred at room temperature for 30 minutes, adjusted to pH 7.4 with sodium hydroxide aqueous solution and then extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. After evaporation of the solvent, the resulting residue was recrystallized from ethanol-ether to yield 198 mg (78%) of the title compound.

후처리

  1. customwas removed by filtration and ethanol
  2. customwas evaporated
  3. temperatureheated
  4. temperatureunder reflux for 18 hours
  5. customAfter evaporation of the solvent
  6. additionthe thus obtained residue was mixed with chloroform
  7. washwashed with water, 10% citric acid aqueous solution and saturated brine in that order
  8. dry with materialdried over anhydrous sodium sulfate
  9. customsubsequently evaporating the solvent
  10. additionThe thus obtained tert-butylcarbamate compound was mixed with 5 ml of concentrated hydrochloric acid
  11. extractionextracted with chloroform
  12. dry with materialthe extract was dried over anhydrous sodium sulfate
  13. customAfter evaporation of the solvent
  14. customthe resulting residue was recrystallized from ethanol-ether

출처 및 근거

ORD 기록
ord-a32e6807456a4d34a01b28d263c6a586
출처 데이터셋
uspto-grants-2002_10
특허 번호
US06469023B1

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