Water → HCID 178497667, compound

HRID 910338Notes

Reaction equation

HRID 910338 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C:12](=[N:15][NH:16][C:17]3[C:18]([OH:32])=[C:19]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([OH:31])=[O:30])[CH:24]=4)[CH:20]=[CH:21][CH:22]=3)[C:11]([CH3:33])=[N:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8].S(=O)(=O)(O)O.O.[CH3:40]COC(C)=O>CO.C1COCC1>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])/[C:12](=[N:15]\[NH:16][C:17]3[C:18]([OH:32])=[C:19]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([O:31][CH3:40])=[O:30])[CH:24]=4)[CH:20]=[CH:21][CH:22]=3)/[C:11]([CH3:33])=[N:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 178433881HCID 178433881, compound

Product 1

HCID 178497667HCID 178497667, compoundYield 83.3%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

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%)

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux
  3. temperatureThe reaction mixture was refluxed overnight
  4. customevaporated
  5. customto obtain an oily residue
  6. customwas formed
  7. customto form a 2-phase system
  8. customthe layers were separated
  9. waitThe organic layer was left for half an hour at room temperature
  10. customresulting in formation of orange crystals
  11. filtrationThe crystals were filtered
  12. washwashed with 2×20 mL EtOAc
  13. customdried in a vacuum oven at 35° C./0 bar for 2 hours

Sources & evidence

ORD record
ord-fbf75ba1ccdd4022b78e4f2077922ab7
Source dataset
uspto-grants-2011_09
Patent number
US08022093B2

Reaction notes

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