Methyl iodide → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595548Notes

Reaction equation

HRID 595548 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][NH:30][C:29](=[O:33])[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.[C:45]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[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][N:30]([CH3:45])[C:29](=[O:33])[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

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 903410595-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)-2-(2-oxo-1,2-dihydropyridin-4-yl)benzofuran-3-carboxamide

Product 1

HCID 778454145-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 53.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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-(2-oxo-1,2-dihydropyridin-4-yl)benzofuran-3-carboxamide (20 mg, 0.03 mmol) and K2CO3 (10 mg, 0.06 mmol) in DMF (1 mL) was added CH3I (5 mg, 0.03 mol) at 0° C. under N2, and then the mixture was stirred for 12 hours at room temperature. After being concentrated in vacuo, the resulting residue was suspended in H2O and extracted with DCM. The combined organic layer was washed with H2O and dried over Na2SO4. After concentration, the residue was purified by prep-HPLC to give the product of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (10 mg, yield: 49%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.7˜28.74 (m, 1H), 8.10 (s, 1H), 7.84˜7.86 (m, 2H), 7.70˜7.72 (m, 1H), 7.59˜7.62 (m, 1H), 7.50˜7.53 (m, 1H), 7.24˜7.28 (m, 1H), 7.23 (s, 1H), 6.96˜7.09 (m, 2H), 6.67˜6.91 (m, 1H), 6.27 (s, 2H), 3.48 (s, 3H), 3.31 (s, 3H), 2.97 (s, 3H), 2.85 (d, J=4.4 Hz, 3H). MS (M+H)+: 628.

Workup

  1. concentrationAfter being concentrated in vacuo
  2. extractionextracted with DCM
  3. washThe combined organic layer was washed with H2O
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentration
  6. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-5f159ba73e444c9999ff803c5e6d6ef7
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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