Cesium carbonate → 5-(6-(4-fluoro-1H-indol-2-yl)-5-(2-hydroxyethyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595765Notes

Reaction equation

HRID 595765 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[CH2:34]O.[F:36][C:37]1[CH:45]=[CH:44][CH:43]=[C:42]2[C:38]=1[CH:39]=[C:40](B1OC(C)(C)C(C)(C)O1)[NH:41]2.[C:55]([O-:58])([O-])=O.[Cs+].[Cs+]>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]>[F:36][C:37]1[CH:45]=[CH:44][CH:43]=[C:42]2[C:38]=1[CH:39]=[C:40]([C:2]1[N:7]=[C:6]([C:8]3[C:9]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:30])=[O:31])=[CH:10][C:11]4[O:15][C:14]([C:16]5[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=5)=[C:13]([C:23]([NH:25][CH3:26])=[O:24])[C:12]=4[CH:27]=3)[CH:5]=[CH:4][C:3]=1[CH2:34][CH2:55][OH:58])[NH:41]2

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 532172124-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indoleHCID 903324365-(6-chloro-5-(hydroxymethyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 903336285-(6-(4-fluoro-1H-indol-2-yl)-5-(2-hydroxyethyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 78%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 5-(6-chloro-5-(hydroxymethyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (300 mg, 0.58 mmol) and 4-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (197 mg, 0.75 mmol) in 1,4-dioxane (5 mL) and water (300 μL) was added Cs2CO3 (377 mg, 1.16 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium chloride (38 mg, 0.06 mmol) under N2 protection. The resulting mixture was heated to 80° C. and stirred at this temperature overnight. The reaction was cooled, filtered through a pad of celite and washed with ethyl acetate. The combined filtrate was evaporated in vacuo. Preparative TLC (eluted with 0-30% acetone/hexane) to provide 5-(6-(4-fluoro-1H-indol-2-yl)-5-(2-hydroxyethyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (280 mg, yield: 78%) MS (M+H)+: 617.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a pad of 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-0de42cca0ae84c50944dc14b0be91a35
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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