反应 #2507856

反应方程式

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-carboxy late

收率 83.3%

溶剂

MeOH THF

反应条件

后处理

1. 1
   温度The suspension was heated
2. 2
   温度to reflux
3. 3
   温度The reaction mixture was refluxed overnight
4. 4
   其他evaporated
5. 5
   其他to obtain an oily residue
6. 6
   其他was formed
7. 7
   其他to form a 2-phase system
8. 8
   其他the layers were separated
9. 9
   workup.WAITThe organic layer was left for half an hour at room temperature
10. 10
    其他resulting in formation of orange crystals
11. 11
    过滤The crystals were filtered
12. 12
    洗涤washed with 2×20 mL EtOAc
13. 13
    其他dried in a vacuum oven at 35° C./0 bar for 2 hours

实验过程

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-carboxy late (Yield: 83.3%); (HPLC: >95%)

来源