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Lithium hydroxide, monohydrate → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxylic acid

HRID 1776908
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HRID 1776908 반응식
[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=7)=[C:24]([C:34]([O:36]C)=[O:35])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1.O[Li].O>O1CCOCC1.O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=7)=[C:24]([C:34]([OH:36])=[O:35])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1
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HCID 168937Lithium hydroxide, monohydrateHCID 86728288methyl 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxylate

생성물 1

HCID 867282875-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxylic acid수율 70%

시약·촉매·용매 1

HCID 21886435
1,4-Dioxane--water (1/1)
용매

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온도
100 °C

실험 절차

To a solution of methyl 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxylate (60 mg, 0.10 mmol) in dioxane/H2O (11 mL/5 mL) was added LiOH.H2O (12.3 mg, 0.30 mol), and the mixture was stirred at 100° C. for 2 hours. After concentrated, the resulting residue was dissolved in H2O, 1 N HCl was added until pH reached 3, and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and filtered. The solvent was removed by distillation to provide 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxylic acid (41 mg, yield: 70%). 1H-NMR (DMSO-d6, 400 MHz) δ 13.36 (s, 1H), 8.26 (s, 1H), 8.13˜8.16 (m, 2H), 8.09 (s, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.61 (d, J=8.4 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.42˜7.46 (m, 2H), 7.25˜7.27 (m, 1H), 7.09 (s, 1H), 6.92˜6.96 (m, 1H), 6.28 (s, 2H), 3.30 (s, 3H), 2.98 (d, 3H). MS (M+H)+: 602.

후처리

  1. concentrationAfter concentrated
  2. dissolutionthe resulting residue was dissolved in H2O
  3. addition1 N HCl was added until pH
  4. extractionthe mixture was extracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customThe solvent was removed by distillation

출처 및 근거

ORD 기록
ord-0b16f8e7952c40e88c6434f90f7b138c
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09265773B2

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