Acetic Acid Mixture with Hydrobromic Acid → 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

HRID 595547Notes

Reaction equation

HRID 595547 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:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:32]=[CH:31][N:30]=[C:29]([O:33]C)[CH:28]=7)=[C:24]([C:35]([NH:37][CH3:38])=[O:36])[C:23]=6[CH:39]=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.Br.CC(O)=O>CC(O)=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:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[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:35]([NH:37][CH3:38])=[O:36])[C:23]=6[CH:39]=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

4

Reactant 2

HCID 21893785Acetic Acid Mixture with Hydrobromic AcidHCID 778451135-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(2-methoxypyridin-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 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-carboxamideYield 52%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(2-methoxypyridin-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (30 mg, 0.05 mmol) in HOAc (1 mL) was added HBr—HOAc (1 mL) at 0° C. Then the mixture was stirred at 80° C. for 2 hours. The solvent was removed by vacuum and NaHCO3 (a.q.) was added. The mixture was extracted with DCM, and the organic phase was dried over Na2SO4. After concentrated in vacuo, 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-6-(N-methylmethylsulfonamido)-2-(2-oxo-1,2-dihydropyridin-4-yl)benzofuran-3-carboxamide (15 mg, yield: 52%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.73˜8.75 (m, 1H), 8.11 (s, 1H), 7.85 (s, 1H), 7.73 (q, J=8.8 Hz, 1H), 7.59˜7.62 (m, 2H), 7.51˜7.61 (m, 2H), 7.25˜7.27 (m, 1H), 7.11 (s, 1H), 6.88˜6.96 (m, 1H), 6.65 (d, J=2.8 Hz, 1H), 6.27 (s, 2H), 3.31 (s, 3H), 2.97 (s, 3H), 2.85 (d, J=4.0 Hz, 3H). MS (M+H)+: 614.

Workup

  1. customThe solvent was removed by vacuum and NaHCO3 (a.q.)
  2. additionwas added
  3. extractionThe mixture was extracted with DCM
  4. dry with materialthe organic phase was dried over Na2SO4
  5. concentrationAfter concentrated in vacuo
  6. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-60bf5092727841d096d0a5ff05b338aa
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

Loading…