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

HRID 1915691Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1915691
[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]

Komponenten

4

Edukt 2

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-2c925343a2a84e178ca2eb96f57791ff
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08614330B2

Notizen zur Reaktion

Wird geladen…