Reaction #41586

Reaction equation

2-hydroxy-benzonitrile

potassium carbonate

5-fluoro-4-(6-ethanesulfonyl-pyridin-3-yloxy)-2-nitro-phenylamine

aniline

pyridine-2-carboxaldehyde

hydrazine monohydrate

→

compound

5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-ethanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

Solvents

N-methylpyrrolidinone

methanol

methanol

methanol

Water

Conditions

Workup

1. 1
   Otherthe reaction liquid
2. 2
   Filtrationthe deposit was taken out through filtration
3. 3
   Otherto obtain a crude product
4. 4
   Otherthe reaction liquid
5. 5
   workup.STIRRINGwas stirred for 1 hour
6. 6
   OtherThe catalyst was removed through filtration
7. 7
   Otherthe solvent was evaporated away under reduced pressure
8. 8
   Otherto obtain 160 mg of a crude product
9. 9
   Otherthe reaction liquid
10. 10
    workup.STIRRINGwas stirred overnight at 80° C
11. 11
    OtherThe solvent was evaporated away under reduced pressure
12. 12
    Otherthe resulting residue was purified
13. 13
    Otherthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)

Procedure

60 mg of 2-hydroxy-benzonitrile and 70 mg of potassium carbonate were added to an N-methylpyrrolidinone (3 ml) solution of 150 mg of 5-fluoro-4-(6-ethanesulfonyl-pyridin-3-yloxy)-2-nitro-phenylamine, and the reaction liquid was stirred at 90° C. for 5 hours. Water was added to the reaction liquid, and the deposit was taken out through filtration to obtain a crude product. 10 mg of developed Raney nickel and 0.12 ml of hydrazine monohydrate were added to a methanol (5 ml) solution of the resulting crude product, and the reaction liquid was stirred for 1 hour. The catalyst was removed through filtration, and the solvent was evaporated away under reduced pressure to obtain 160 mg of a crude product. 0.20 ml of 1 M methanol solution of aniline and pyridine-2-carboxaldehyde (1/1) was added to a methanol (3 ml) solution of 35 mg of the resulting crude product, and the reaction liquid was stirred overnight at 80° C. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1) to obtain the entitled compound as a yellow solid.

Source