反応 #41795

反応方程式

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

溶媒

ethyl acetate

THF

反応条件

後処理

1. 1
   workup.ADDITIONwere added
2. 2
   workup.ADDITIONwas added
3. 3
   洗浄washed with water
4. 4
   洗浄The aqueous layer was washed with ethyl acetate
5. 5
   乾燥dried over MgSO4
6. 6
   ろ過filtered
7. 7
   濃縮concentrated
8. 8
   workup.ADDITIONAcetic acid was added to the residue
9. 9
   濃縮is concentrated
10. 10
    その他the residue purified by reverse phase HPLC

実験手順

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.

出典