Reaktion #333404

Reaktionsgleichung

DIPEA

HATU

1-(4-bromo-phenyl)-cyclopropanamine

2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

→

2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(4-bromo-phenyl)-cyclopropyl]-amide

Ausbeute 91.2%

Lösungsmittel

water

EA

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionthe organic compound was extracted into EtOAc (3×25 mL)
2. 2
   WaschenThe combined extracts were washed with brine solution
3. 3
   Trocknendried over anhydrous MgSO4
4. 4
   FiltrationFiltration of the drying agent and concentration of the filtrate
5. 5
   Sonstigegave the crude product which
6. 6
   Sonstigewas purified
7. 7
   Wascheneluting with EtOAc in hexanes (0-60%) in 10 minutes
8. 8
   Sonstigethe solvent was removed under vacuum

Vorschrift

To a stirred suspension of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (150 mg, 0.34 mmol) in DMF (5 mL) were added HATU (258 mg, 0.68 mmol) and 1-(4-bromo-phenyl)-cyclopropanamine (108 mg, 0.51 mmol) followed by DIPEA (0.24 mL, 1.36 mmol) at room temperature under nitrogen atmosphere. The resulting light yellow solution was stirred for 15 h by which time TLC analysis (Hex:EA, 1:1, Rf=0.5) indicated the presence of a new spot. Then, the reaction mixture was diluted with water and the organic compound was extracted into EtOAc (3×25 mL). The combined extracts were washed with brine solution and then dried over anhydrous MgSO4. Filtration of the drying agent and concentration of the filtrate gave the crude product which was purified using by ISCO column chromatography (40 g) eluting with EtOAc in hexanes (0-60%) in 10 minutes. The desired fractions were combined and the solvent was removed under vacuum to obtain 197 mg (91%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(4-bromo-phenyl)-cyclopropyl]-amide as a off-white solid.

Quelle