HCID 90341045, compound → HCID 77845567, compound

HRID 595561Notes

Reaction equation

HRID 595561 reaction equation
[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

Participants

5

Reactant 2

HCID 90341045HCID 90341045, compoundHCID 178526069HCID 178526069, compound

Product 2

HCID 77845567HCID 77845567, compoundHCID 90333930HCID 90333930, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d5bb8ef252174fec8ba0bb7812acd462
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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