Reacción #333618

Ecuación de reacción

Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

potassium carbonate

2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

→

N-tert-butyl-2-(2-methyl-1H-indol-7-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Rendimiento 73.6%

Disolventes

ethyl acetate ether

dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowater (0.5 mL), then the reaction was purged with nitrogen for 1 minute
2. 2
   Temperaturathe reaction was heated at 80° C. for an additional 2 h
3. 3
   TemperaturaThe reaction mixture was cooled
4. 4
   Lavadowashed water and brine
5. 5
   Secadodried (MgSO4)
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   OtroThe crude residue was purified by chromatography (silica gel, 3-15% ethyl acetate in hexanes)

Procedimiento

2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (79 mg, 185 μmol), potassium carbonate (51.1 mg, 370 μmol) and 2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (95.1 mg, 370 μmol) were dissolved in dioxane (5 mL) and water (0.5 mL), then the reaction was purged with nitrogen for 1 minute. Tetrakis(triphenylphosphine)palladium(0) (21.4 mg, 18.5 μmol) was then added, and the reaction was placed under a nitrogen atmosphere and the mixture heated at to 80° C. for 2 h. Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (45 mg), was added and the reaction was heated at 80° C. for an additional 2 h. The reaction mixture was cooled, diluted with ethyl acetate/ether (ca 3:1), washed water and brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by chromatography (silica gel, 3-15% ethyl acetate in hexanes) to give N-tert-butyl-2-(2-methyl-1H-indol-7-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (65 mg) as an oil. MS (M+H)+=478.3.

Fuente