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

HRID 13514Notes

Reaction equation

HRID 13514 reaction equation
[F:1][C:2]([F:14])([F:13])[S:3][C:4]1[CH:5]=[C:6]([N:10]=[C:11]=S)[CH:7]=[CH:8][CH:9]=1.[OH:15][CH2:16][CH2:17][NH:18][C:19]([C:21]1[CH:26]=[C:25]([O:27][C:28]2[CH:33]=[CH:32][C:31]([NH:34][CH3:35])=[C:30]([NH2:36])[CH:29]=2)[CH:24]=[CH:23][N:22]=1)=[O:20]>CO>[OH:15][CH2:16][CH2:17][NH:18][C:19]([C:21]1[CH:26]=[C:25]([O:27][C:28]2[CH:33]=[CH:32][C:31]3[N:34]([CH3:35])[C:11]([NH:10][C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([S:3][C:2]([F:14])([F:13])[F:1])[CH:5]=4)=[N:36][C:30]=3[CH:29]=2)[CH:24]=[CH:23][N:22]=1)=[O:20]

Participants

4

Reactant 2

HCID 44110273-(Trifluoromethylthio)phenyl isothiocyanateHCID 210372884-(3-Amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide

Product 1

HCID 220411304-[1-Methyl-2-(3-trifluoromethylsulfanyl-phenylamino)-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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.

Workup

  1. customThe reaction was partitioned with EtOAc and water
  2. filtrationfiltered through Celite
  3. customThe layers were separated
  4. extractionThe resulting aqueous phase was extracted with EtOAc
  5. filtrationthe mixture was filtered through Celite
  6. customThe phases were separated
  7. extractionthe aqueous phase was again extracted
  8. filtrationfiltered
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a brown solid
  14. customThe crude residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-49bcfd9ac178422f933ccdfdadc96f3b
Source dataset
uspto-grants-2010_06
Patent number
US07728010B2

Reaction notes

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