HCID 90341045, 화합물 → HCID 77845567, 화합물

HRID 595561노트

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HRID 595561 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](=[O:33])[NH:29][CH:28]=7)=[C:24]([C:34]([NH:36][CH3:37])=[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.Cl[C:46](C(O[Na])=O)([F:48])[F:47]>CC#N>[F:47][CH:46]([F:48])[O:33][C:30]1[N:29]=[CH:28][C:27]([C:25]2[O:26][C:22]3[CH:21]=[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])[C:19]([C:16]4[CH:17]=[CH:18][C:13]5[O:12][CH2:11][N:6]6[C:7]7[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[C:3]=7[CH:4]=[C:5]6[C:14]=5[N:15]=4)=[CH:38][C:23]=3[C:24]=2[C:34]([NH:36][CH3:37])=[O:35])=[CH:32][CH:31]=1.[F:47][CH:46]([F:48])[N:29]1[C:30](=[O:33])[CH:31]=[CH:32][C:27]([C:25]2[O:26][C:22]3[CH:21]=[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])[C:19]([C:16]4[CH:17]=[CH:18][C:13]5[O:12][CH2:11][N:6]6[C:7]7[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[C:3]=7[CH:4]=[C:5]6[C:14]=5[N:15]=4)=[CH:38][C:23]=3[C:24]=2[C:34]([NH:36][CH3:37])=[O:35])=[CH:28]1

참가 물질

5

반응물 2

HCID 90341045HCID 90341045, 화합물HCID 178526069HCID 178526069, 화합물

생성물 2

HCID 77845567HCID 77845567, 화합물HCID 90333930HCID 90333930, 화합물

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

To a suspension of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-oxo-1,6-dihydropyridin-3-yl)benzofuran-3-carboxamide (40 mg, 0.06 mmol) in MeCN (5 mL) was added F2ClCCOONa (20 mg, 0.13 mol) under N2, and then the mixture was stirred at 100° C. for 12 hours. After concentrated in vacuo, the resulting residue was suspended in H2O and extracted with DCM. The combined organic layer was washed with H2O, brine, dried over Na2SO4, filtrated and concentrated in vacuo. The residue was purified by prep-HPLC to give the product of 2-(6-(difluoromethoxy)pyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide and 2-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide. 2-(6-(difluoromethoxy)pyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 47%). 1H-NMR (CDCl3, 400 MHz) δ 8.84 (d, J=2.0 Hz, 1H), 8.43˜8.47 (m, 1H), 7.96 (s, 1H), 7.73 (s, 0.25H), 7.69 (s, 1H), 7.55 (s, 0.5H), 7.50˜7.52 (m, 2H), 7.37 (s, 0.25H), 7.20˜7.24 (m, 2H), 7.13 (d, J=4.4 Hz, 1H), 7.04 (d, J=4.2 Hz, 1H), 6.84˜6.87 (m, 1H), 6.07 (s, 1H), 5.99 (s, 2H), 3.35 (s, 3H), 3.05 (d, J=4.8 Hz, 3H), 2.78 (s, 3H). MS (M+H)+: 664. 2-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (10 mg, yield: 23%). 1H-NMR (CDCl3, 400 MHz) δ 8.67 (d, J=2.0 Hz, 1H), 8.12˜8.15 (m, 1H), 7.92 (s, 1H), 7.76 (s, 0.25H), 7.69 (s, 0.5H), 7.61 (s, 0.25H), 7.51˜7.53 (m, 2H), 7.50 (s, 1H), 7.21˜7.24 (m, 2H), 7.14 (d, J=8.0 Hz, 1H), 6.84˜6.89 (m, 1H), 6.67 (d, J=8.0 Hz, 1H), 6.14 (s, 1H), 6.02 (s, 2H), 3.35 (s, 3H), 3.08 (d, J=4.8 Hz, 3H), 2.81 (s, 3H). MS (M+H)+: 664.

후처리

  1. concentrationAfter concentrated in vacuo
  2. extractionextracted with DCM
  3. washThe combined organic layer was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltrated
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by prep-HPLC

출처 및 근거

ORD 기록
ord-d5bb8ef252174fec8ba0bb7812acd462
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242998B2

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