Acetonitrile → 7-[(3R)-3-(1-tert-Butoxycarbonylaminocyclopropyl)-pyrrolidin-1-yl]-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid

HRID 254869노트

반응식

HRID 254869 반응식
C(#N)C.F[C:5]1[C:14]([O:15][CH3:16])=[C:13]2[C:8]([C:9](=[O:24])[C:10]([C:21]([OH:23])=[O:22])=[CH:11][N:12]2[C@@H:17]2[CH2:19][C@@H:18]2[F:20])=[CH:7][CH:6]=1.Cl.C(N(CC)CC)C.C(O)(=O)C(O)=O.[NH:39]1[CH2:43][CH2:42][C@@H:41]([C:44]2([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:46][CH2:45]2)[CH2:40]1>C(N(CC)CC)C>[C:50]([O:49][C:48]([NH:47][C:44]1([C@@H:41]2[CH2:42][CH2:43][N:39]([C:5]3[C:14]([O:15][CH3:16])=[C:13]4[C:8]([C:9](=[O:24])[C:10]([C:21]([OH:23])=[O:22])=[CH:11][N:12]4[C@@H:17]4[CH2:19][C@@H:18]4[F:20])=[CH:7][CH:6]=3)[CH2:40]2)[CH2:45][CH2:46]1)=[O:54])([CH3:53])([CH3:51])[CH3:52]

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 11130Triethylamine hydrochlorideHCID 120824067-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acidHCID 67340995(R)-tert-Butyl (1-(pyrrolidin-3-yl)cyclopropyl)carbamate oxalate

생성물 1

HCID 579759627-[(3R)-3-(1-tert-Butoxycarbonylaminocyclopropyl)-pyrrolidin-1-yl]-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid수율 94%

시약·촉매·용매 1

HCID 8471Triethylamine용매

실험 절차

An acetonitrile solution (45 mL) containing 7-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (3 g), triethylamine hydrochloride (2.8 g), and boron trifluoride-tetrahydrofuran complex (2.84 g) was stirred at room temperature for 30 minutes. tert-Butyl {1-[(3R)-pyrrolidin-3-yl]cyclopropyl}carbamate oxalic acid salt (3.54 g) and triethylamine (5.71 mL) were further added to reaction mixture, followed by stirring for 10 hours at the same temperature. The solvent was evaporated under reduced pressure, and methanol (30 mL) was added to the residue. The mixture was refluxed for 12 hours, and the solvent was evaporated under reduced pressure. 80% Hydrated methanol (20 mL) was added to the residue, and the pH of the product was adjusted to 7 by use of 5N aqueous sodium hydroxide solution, followed by stirring at 60° C. for 30 minutes and at room temperature for 16 hours. The thus-produced crystals were recovered through filtration and dried, to thereby yield 4.79 g of the title compound (yield: 94%).

후처리

  1. stirringby stirring for 10 hours at the same temperature
  2. customThe solvent was evaporated under reduced pressure, and methanol (30 mL)
  3. additionwas added to the residue
  4. temperatureThe mixture was refluxed for 12 hours
  5. customthe solvent was evaporated under reduced pressure
  6. addition80% Hydrated methanol (20 mL) was added to the residue
  7. stirringby stirring at 60° C. for 30 minutes and at room temperature for 16 hours
  8. filtrationThe thus-produced crystals were recovered through filtration
  9. customdried

출처 및 근거

ORD 기록
ord-d085afb6a645471e989018fecfee2b58
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07875722B2

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