Reaction #41792

Reaction equation

3-(trifluoromethylthio)phenylisothiocyanate

4-(3-amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide

→

4-[1-Methyl-2-(3-trifluoromethylsulfanyl-phenylamino)-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide

Solvents

MeOH

Conditions

Workup

1. 1
   OtherThe reaction was partitioned with EtOAc and water
2. 2
   Filtrationfiltered through Celite
3. 3
   OtherThe layers were separated
4. 4
   ExtractionThe resulting aqueous phase was extracted with EtOAc
5. 5
   Filtrationthe mixture was filtered through Celite
6. 6
   OtherThe phases were separated
7. 7
   Extractionthe aqueous phase was again extracted
8. 8
   Filtrationfiltered
9. 9
   WashThe combined organic layers were washed with brine
10. 10
    Dryingdried (MgSO4)
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated
13. 13
    Otherto give a brown solid
14. 14
    OtherThe crude residue was purified by reverse phase HPLC

Procedure

A flask was charged with 3-(trifluoromethylthio)phenylisothiocyanate (1 eq), 4-(3-amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide (1 eq), and MeOH. The reaction was maintained at rt overnight. Ferric chloride, (1.5 eq) was added and the resulting red reaction mixture was stirred overnight. The reaction was partitioned with EtOAc and water, and filtered through Celite. The layers were separated and the aqueous phase was neutralized with saturated Na2CO3 solution. The resulting aqueous phase was extracted with EtOAc and the mixture was filtered through Celite. The phases were separated and the aqueous phase was again extracted and filtered. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated to give a brown solid. The crude residue was purified by reverse phase HPLC. LCMS m/z 504.1 (MH+), tR=3.7 min.

Source