HCID 90341045、化合物 → HCID 77845567、化合物

HRID 595561ノート

反応式

HRID 595561 の反応式
[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

参加物

5

反応物 2

HCID 90341045HCID 90341045、化合物HCID 178526069HCID 178526069、化合物

生成物 2

HCID 77845567HCID 77845567、化合物HCID 90333930HCID 90333930、化合物

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d5bb8ef252174fec8ba0bb7812acd462
出典データセット
uspto-grants-2016_01
特許番号
US09242998B2

反応ノート

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