4-Fluorophenyl isothiocyanate → 4-[2-(4-Fluoro-phenylamino)-1-methyl-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid tert-butyl ester

HRID 13515Notes

Reaction equation

HRID 13515 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=S)=[CH:4][CH:3]=1.[C:11]([O:15][C:16]([C:18]1[CH:23]=[C:22]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][CH3:32])=[C:27]([NH2:33])[CH:26]=2)[CH:21]=[CH:20][N:19]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>CO>[C:11]([O:15][C:16]([C:18]1[CH:23]=[C:22]([O:24][C:25]2[CH:30]=[CH:29][C:28]3[N:31]([CH3:32])[C:9]([NH:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[N:33][C:27]=3[CH:26]=2)[CH:21]=[CH:20][N:19]=1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

4

Reactant 2

HCID 152414-Fluorophenyl isothiocyanateHCID 22040526Tert-butyl4-[3-amino-4-(methylamino)phenoxy]pyridine-2-carboxylate

Product 1

HCID 210373684-[2-(4-Fluoro-phenylamino)-1-methyl-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A round bottom flask was charged with 4-fluorophenylisothiocyanate (1 eq), 4-(3-Amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid tert-butyl ester (1 eq), and MeOH. The reaction was maintained stirring at room temperature overnight. Ferric chloride, (1.5 eq) was added and the resulting 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 over MgSO4, filtered, and concentrated to give a brown solid. The crude residue was purified by trituration in hot toluene to furnish the desired product. LCMS m/z 435.6 (MH+), tR=2.12 min.

Workup

  1. temperatureThe reaction was maintained
  2. stirringthe resulting mixture was stirred overnight
  3. customThe reaction was partitioned with EtOAc and water
  4. filtrationfiltered through Celite
  5. customThe layers were separated
  6. extractionThe resulting aqueous phase was extracted with EtOAc
  7. filtrationthe mixture was filtered through Celite
  8. customThe phases were separated
  9. extractionthe aqueous phase was again extracted
  10. filtrationfiltered
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto give a brown solid
  16. customThe crude residue was purified by trituration in hot toluene

Sources & evidence

ORD record
ord-80899cb114014d05a92452156dc1b435
Source dataset
uspto-grants-2010_06
Patent number
US07728010B2

Reaction notes

Loading…