تفاعل #41795

معادلة التفاعل

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

المذيبات

ethyl acetate

THF

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwere added
2. 2
   workup.ADDITIONwas added
3. 3
   غسيلwashed with water
4. 4
   غسيلThe aqueous layer was washed with ethyl acetate
5. 5
   تجفيفdried over MgSO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated
8. 8
   workup.ADDITIONAcetic acid was added to the residue
9. 9
   تركيزis concentrated
10. 10
    أخرىthe residue purified by reverse phase HPLC

الإجراء التجريبي

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.

المصدر