Reaktion #41795

Reaktionsgleichung

sodium acetate

phenylenediamine

4-[2-(4-Fluoro-phenylamino)-1-methyl-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid

EDC-HCl

HOAT

diisopropylethylamine

→

desired product

{5-[2-(1H-Benzoimidazol-2-yl)-pyridin-4-yloxy]-1-methyl-1H-benzoimidazol-2-yl}-(4-fluoro-phenyl)-amine

Lösungsmittel

ethyl acetate

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added
2. 2
   workup.ADDITIONwas added
3. 3
   Waschenwashed with water
4. 4
   WaschenThe aqueous layer was washed with ethyl acetate
5. 5
   Trocknendried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   workup.ADDITIONAcetic acid was added to the residue
9. 9
   Einengenis concentrated
10. 10
    Sonstigethe residue purified by reverse phase HPLC

Vorschrift

To a suspension of 4-[2-(4-Fluoro-phenylamino)-1-methyl-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid (1 eq) in dry THF, EDC-HCl (1.2 eq), HOAT (1.2 eq), and diisopropylethylamine (3 eq) were added. The suspension was stirred for 10 minutes whereupon phenylenediamine (1.1 eq) was added and the solution is allowed to stir overnight. The mixture was then diluted with ethyl acetate and washed with water. The aqueous layer was washed with ethyl acetate, the organic layers combined, dried over MgSO4, filtered, and concentrated. Acetic acid was added to the residue followed by sodium acetate (1.1 eq). The mixture was heated for 3 hours at 70° C., whereupon the solution is concentrated and the residue purified by reverse phase HPLC to afford the desired product. LCMS m/z 451.5 (MH+), tR=1.92 min.

Quelle