Reaktion #473554

Reaktionsgleichung

Water

3′-{N′-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid

EtOAc

sulfuric acid

→

(Z)-methyl 3′-(2-(1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl)-2′-hydroxybiphenyl-3-carboxylate

Ausbeute 83.3%

Lösungsmittel

MeOH THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe suspension was heated
2. 2
   Temperaturto reflux
3. 3
   TemperaturThe reaction mixture was refluxed overnight
4. 4
   Sonstigeevaporated
5. 5
   Sonstigeto obtain an oily residue
6. 6
   Sonstigewas formed
7. 7
   Sonstigeto form a 2-phase system
8. 8
   Sonstigethe layers were separated
9. 9
   workup.WAITThe organic layer was left for half an hour at room temperature
10. 10
    Sonstigeresulting in formation of orange crystals
11. 11
    FiltrationThe crystals were filtered
12. 12
    Waschenwashed with 2×20 mL EtOAc
13. 13
    Sonstigedried in a vacuum oven at 35° C./0 bar for 2 hours

Vorschrift

Pure 3′-{N′-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid (Eltrombopag) (20 g, 0.045 mol) was suspended in a mixture of MeOH/THF=1/1 (400 mL). The suspension was heated to reflux and sulfuric acid (5 mL) was added drop wise. The reaction mixture was refluxed overnight, cooled to room temperature and evaporated to obtain an oily residue. Water (200 ml) was added to the and a thick suspension was formed. EtOAc (200 ml) was added to form a 2-phase system and the layers were separated. The organic layer was left for half an hour at room temperature resulting in formation of orange crystals. The crystals were filtered, washed with 2×20 mL EtOAc and dried in a vacuum oven at 35° C./0 bar for 2 hours, giving 17.17 g of (Z)-methyl 3′-(2-(1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl)-2′-hydroxybiphenyl-3-carboxylate (Yield: 83.3%); (HPLC: >95%)

Quelle