4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indole → (E)-5-(5-(2-ethoxyvinyl)-6-(4-fluoro-1H-indol-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595756Notes

Reaction equation

HRID 595756 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].[F:39][C:40]1[CH:48]=[CH:47][CH:46]=[C:45]2[C:41]=1[CH:42]=[C:43](B1OC(C)(C)C(C)(C)O1)[NH:44]2>O1CCOCC1.O.[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]>[CH2:37]([O:36]/[CH:35]=[CH:34]/[C:3]1[CH:4]=[CH:5][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]([NH:25][CH3:26])=[O:24])[C:12]=3[CH:27]=2)=[N:7][C:2]=1[C:43]1[NH:44][C:45]2[C:41]([CH:42]=1)=[C:40]([F:39])[CH:48]=[CH:47][CH:46]=2)[CH3:38]

Participants

6

Reactant 2

HCID 532172124-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indoleHCID 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 90333424(E)-5-(5-(2-ethoxyvinyl)-6-(4-fluoro-1H-indol-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 28%

Reagents, catalysts & solvents 3

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of (E)-5-(6-chloro-5-(2-ethoxyvinyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (200 mg, 0.36 mmol) and 4-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (140 mg, 0.54 mmol) in 1,4-dioxane (3 mL) and water (200 μl) was added CS2CO3 (234 mg, 0.72 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium chloride (24 mg, 0.04 mmol) under N2 protection. The resulting mixture was heated to 90° C. and stirred at this temperature for 3 hours. The reaction was cooled, filtered through a pad of the celite and washed with ethyl acetate. The combined filtrate was evaporated in vacuo. Preparative TLC (eluted with 0-30% acetone/hexane) provided (E)-5-(5-(2-ethoxyvinyl)-6-(4-fluoro-1H-indol-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (65 mg, yield: 28%) MS (M+H)+: 657.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a pad of the celite
  3. washwashed with ethyl acetate
  4. customThe combined filtrate was evaporated in vacuo
  5. washPreparative TLC (eluted with 0-30% acetone/hexane)

Sources & evidence

ORD record
ord-dc74c428ccd9492c95b7464f32c635f9
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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