반응 #41795

반응 방정식

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

용매

ethyl acetate

THF

반응 조건

후처리

1. 1
   workup.ADDITIONwere added
2. 2
   workup.ADDITIONwas added
3. 3
   세척washed with water
4. 4
   세척The aqueous layer was washed with ethyl acetate
5. 5
   건조dried over MgSO4
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   workup.ADDITIONAcetic acid was added to the residue
9. 9
   농축is concentrated
10. 10
    기타the residue purified by reverse phase HPLC

실험 절차

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.

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