Reacción #333447

Ecuación de reacción

2-(6-Fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide

Sodium hydride

1-(2-Bromoethyl)pyrrolidine hydrochloride

→

2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide

Rendimiento 91.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto give a yellow solution
2. 2
   Otroteh reaction
3. 3
   workup.STIRRINGwas stirred at 0° C. for 30 min
4. 4
   Temperaturathen warmed to room temperature
5. 5
   workup.STIRRINGThe reaction mixture was stirred for 2 h
6. 6
   Otrothen quenched with 5 mL of brine and 10 mL of water
7. 7
   Extracciónextracted with ethyl acetate (2×30 mL)
8. 8
   LavadoThe combined organic layers were washed with water and brine
9. 9
   Secadothen dried with MgSO4
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated in vacuo
12. 12
    OtroThe residue was purified by silica gel chromatography (0-10% methanol in dichloromethane)

Procedimiento

2-(6-Fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide (70 mg, 0.13 mmol) was combined with DMF (2 mL) at 0° C. to give a yellow solution. Sodium hydride (60% in mineral oil, 14 mg, 0.385 mmol) was added and the reaction was stirred at 0° C. for 10 min. 1-(2-Bromoethyl)pyrrolidine hydrochloride (41 mg, 0.19 mmol) was added and teh reaction was stirred at 0° C. for 30 min then warmed to room temperature. The reaction mixture was stirred for 2 h then quenched with 5 mL of brine and 10 mL of water and extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with water and brine then dried with MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (0-10% methanol in dichloromethane) to afford 75 mg (91%) of 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide as a foaming solid. MS: (M+H)+=643.

Fuente