4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indole → 5-(10-fluoro-5-hydroxy-5H-pyrido[2',3':3,4]pyrrolo[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595763Notes

Reaction equation

HRID 595763 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]=[O:35].[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>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[C:38]2[CH:39]=[C:40]3[C:2]4[N:7]=[C:6]([C:8]5[C:9]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:30])=[O:31])=[CH:10][C:11]6[O:15][C:14]([C:16]7[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=7)=[C:13]([C:23]([NH:25][CH3:26])=[O:24])[C:12]=6[CH:27]=5)[CH:5]=[CH:4][C:3]=4[CH:34]([OH:35])[N:41]3[C:42]=2[CH:43]=[CH:44][CH:45]=1

Participants

6

Reactant 2

HCID 532172124-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indoleHCID 903324705-(6-chloro-5-formylpyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 903334995-(10-fluoro-5-hydroxy-5H-pyrido[2',3':3,4]pyrrolo[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 22.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a degassed solution of 5-(6-chloro-5-formylpyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (150 mg, 0.29 mmol) and 4-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (94 mg, 0.35 mmol) in 1,4-dioxane (3 mL) and water (200 μL) was added CS2CO3 (189 mg, 0.58 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium chloride (30 mg, 0.05 mmol) under N2 protection. The resulting mixture was heated to 90° C. and stirred for 3 hours. 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 (30% ethyl acetate/DCM) to provide 5-(10-fluoro-5-hydroxy-5H-pyrido[2′,3′:3,4]pyrrolo[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (40 mg, yield: 22%) MS (M+H)+: 615.

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 (30% ethyl acetate/DCM)

Sources & evidence

ORD record
ord-fb0614d5aa844106b17a08e8bedf0535
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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