Cesium carbonate → (E)-5-(6-chloro-5-(2-ethoxyvinyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595748Notes

Reaction equation

HRID 595748 reaction equation
Br[C:2]1[N:7]=[C:6]([Cl:8])[C:5](/[CH:9]=[CH:10]/[O:11][CH2:12][CH3:13])=[CH:4][CH:3]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[O:22][C:23]3[CH:33]=[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])[C:31](B4OC(C)(C)C(C)(C)O4)=[CH:30][C:24]=3[C:25]=2[C:26]([NH:28][CH3:29])=[O:27])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>O>[Cl:8][C:6]1[N:7]=[C:2]([C:31]2[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])=[CH:33][C:23]3[O:22][C:21]([C:18]4[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=4)=[C:25]([C:26]([NH:28][CH3:29])=[O:27])[C:24]=3[CH:30]=2)[CH:3]=[CH:4][C:5]=1/[CH:9]=[CH:10]/[O:11][CH2:12][CH3:13]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 90332603(E)-6-bromo-2-chloro-3-(2-ethoxyvinyl)pyridine

Product 1

HCID 90332463(E)-5-(6-chloro-5-(2-ethoxyvinyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of (E)-6-bromo-2-chloro-3-(2-ethoxyvinyl)pyridine (3.37 g, 12.84 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (6.45 g, 12.84 mmol), cesium carbonate (10.46 g, 32.1 mmol), and 1,1′ Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.524 g, 0.642 mmol) was added 1,4-Dioxane (83 mL) followed by H2O (8.34 mL). A steady stream of N2 was bubbled through the reaction mixture for 7 minutes then the mixture was heated to 60° C. for 16 h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed successively with H2O (1×) and brine (1×). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The solid residue was triturated with EtOAc and further purified by silica gel column chromatography using a gradient of 0-30% EtOAc/CH2Cl2 as eluent. Further purification by silica gel column chromatography with a gradient of 0-100% EtOAc/Hexanes as eluent provided the title compound as a tan solid. 1H NMR δ (ppm) (CHCl3-d): 8.03˜7.97 (3H, m), 7.79 (1H, d, J=7.96 Hz), 7.69 (1H, s), 7.52 (1H, d, J=7.50 Hz), 7.28˜7.00 (2H, m), 7.11 (1H, d, J=13.00 Hz), 6.12 (1H, d, J=13.00 Hz), 5.91 (1H, br s), 4.04 (2H, q, J=7.04 Hz), 3.24 (3H, s), 3.03 (3H, d, J=4.87 Hz), 2.89 (3H, s), 1.44 (3H, t, J=7.00). MS (M+H): 557.

Workup

  1. customA steady stream of N2 was bubbled through the reaction mixture for 7 minutes
  2. temperatureThe mixture was cooled to ambient temperature
  3. additiondiluted with EtOAc
  4. washwashed successively with H2O (1×) and brine (1×)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe solid residue was triturated with EtOAc
  9. customfurther purified by silica gel column chromatography
  10. customFurther purification by silica gel column chromatography with a gradient of 0-100% EtOAc/Hexanes as eluent

Sources & evidence

ORD record
ord-e0e31ad25e894a60bc9931d7c618c808
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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