Cesium carbonate → (E)-tert-butyl 2-(3-(2-ethoxyvinyl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-2-yl)-3-methyl-1H-indole-1-carboxylate

HRID 595749Notes

Reaction equation

HRID 595749 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:31])=[O:30])=[CH:10][C:11]3[O:15][C:14]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)=[C:13]([C:23]([NH:25][CH3:26])=[O:24])[C:12]=3[CH:27]=2)[CH:5]=[CH:4][C:3]=1/[CH:34]=[CH:35]/[O:36][CH2:37][CH3:38].[CH3:39][C:40]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[N:42]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C:41]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].O>[CH2:37]([O:36]/[CH:35]=[CH:34]/[C:3]1[C:2]([C:41]2[N:42]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C:43]3[C:48]([C:40]=2[CH3:39])=[CH:47][CH:46]=[CH:45][CH:44]=3)=[N:7][C:6]([C:8]2[C:9]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:30])=[O:31])=[CH:10][C:11]3[O:15][C:14]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)=[C:13]([C:23](=[O:24])[NH:25][CH3:26])[C:12]=3[CH:27]=2)=[CH:5][CH:4]=1)[CH3:38]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 67148908tert-butyl 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylateHCID 90332463(E)-5-(6-chloro-5-(2-ethoxyvinyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 90333599(E)-tert-butyl 2-(3-(2-ethoxyvinyl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-2-yl)-3-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of (E)-5-(6-chloro-5-(2-ethoxyvinyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (150 mg, 0.269 mmol), tert-butyl 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (144 mg, 0.403 mmol), cesium carbonate (175 mg, 0.538 mmol), and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (17.5 mg, 0.027 mmol) was added 1,4-dioxane (2.44 mL) and H2O (0.244 mL). A steady stream of N2 was bubbled through the reaction mixture for 5 minutes then the mixture was heated to 90° C. for 10 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 residue was purified by silica gel column chromatography using a gradient of 0-100% EtOAc/Hexanes as eluent. MS (M+H): 753.

Workup

  1. customA steady stream of N2 was bubbled through the reaction mixture for 5 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 residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8a3172d6b4e444b1a86ba2dd6f88cb19
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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