Triethylamine → 7-{3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidin-1-yl}-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 600911노트

반응식

HRID 600911 반응식
F[C:2]1[C:11]([O:12][CH3:13])=[C:10]2[C:5]([C:6](=[O:21])[C:7]([C:18]([OH:20])=[O:19])=[CH:8][N:9]2[C@@H:14]2[CH2:16][C@@H:15]2[F:17])=[CH:4][CH:3]=1.[C:22]([O:26][C:27]([NH:29][C:30]1([C@@H:34]2[CH2:38][CH2:37][NH:36][CH2:35]2)[CH2:33][CH2:32][CH2:31]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(N(CC)CC)C>CS(C)=O>[C:22]([O:26][C:27]([NH:29][C:30]1([C@@H:34]2[CH2:38][CH2:37][N:36]([C:2]3[C:11]([O:12][CH3:13])=[C:10]4[C:5]([C:6](=[O:21])[C:7]([C:18]([OH:20])=[O:19])=[CH:8][N:9]4[C@@H:14]4[CH2:16][C@@H:15]4[F:17])=[CH:4][CH:3]=3)[CH2:35]2)[CH2:31][CH2:32][CH2:33]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 120824067-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acidHCID 672716403-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidine

생성물 1

HCID 672704287-{3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidin-1-yl}-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
80 °C

실험 절차

A mixture of 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (290 mg, 0.98 mmol), 3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidine (283 mg, 1.18 mmol), triethylamine (0.409 ml, 2.94 mmol), and dimethyl sulfoxide (5 ml) was stirred for 112 hours while heating in an oil bath at 80° C. under an argon-replaced atmosphere. After evaporating the solvent, the residue was partitioned in chloroform (50 ml) and 10% aqueous citric acid solution (30 ml), and after separating the organic layer, the organic layer was washed with saturated saline solution (30 ml). The organic layer obtained was then dried over anhydrous sodium sulfate, and after removing the drying agent by filtration, the solvent was evaporated under a reduced pressure. The residue was subject to a silica gel chromatography and a crude 7-{3-(R)-[1-(tert-butoxycarbonylamino)cyclobutyl]pyrrolidin-1-yl}-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid was thereby obtained from a chloroform:methanol=20:1 eluate.

후처리

  1. customAfter evaporating the solvent
  2. customthe residue was partitioned in chloroform (50 ml)
  3. custom10% aqueous citric acid solution (30 ml), and after separating the organic layer
  4. washthe organic layer was washed with saturated saline solution (30 ml)
  5. customThe organic layer obtained
  6. dry with materialwas then dried over anhydrous sodium sulfate
  7. customafter removing the drying agent
  8. filtrationby filtration
  9. customthe solvent was evaporated under a reduced pressure

출처 및 근거

ORD 기록
ord-72f29c1a95f1449fbd8306720b724087
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902226B2

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