反应详情

温度

0 °C

Bromovaleryl chloride (1.62 mL, 12.12 mmol) was dissolved in DMA (50 mL). To this, a solution of 5-thiophen-2-yl-2H-pyrazol-3-ylamine (2 g, 12.12 mmol) and DIEA (2.1 mL, 12.12 mmol) was added portionwise at 0° C. The reaction mixture was left stirring 1 hour at 0° C. and then for 2 hours at room temperature. After a total of 3 hours, PS-Trisamine (1 g, ˜4 mmol/g) was added to the mixture and left stirring for 2 hours. Then, N-acetylhomopiperazine (4.3 g, 30.3 mmol) was added and the mixture was left stirring at room temperature for a further 60 hours. After DMA evaporation under reduced pressure, water was added (50 mL) and this was extracted with ethyl acetate (3×30 mL). The aqueous layer was basified with solid NaOH and extracted with ethyl acetate at pH=10 and then again at pH=11. All the organic phases were reunited, dried and evaporated. The residue was purified by silica chromatography eluting with a gradient of ethyl acetate/methanol 9:1 up to ethyl acetate/methanol 8:2, to give the title compound as yellowish oil (800 mg, 17%).

1. waitThe reaction mixture was left
2. waitfor 2 hours at room temperature
3. waitleft
4. stirringstirring for 2 hours
5. waitthe mixture was left
6. stirringstirring at room temperature for a further 60 hours
7. customAfter DMA evaporation under reduced pressure, water
8. additionwas added (50 mL)
9. extractionthis was extracted with ethyl acetate (3×30 mL)
10. extractionextracted with ethyl acetate at pH=10
11. customdried
12. customevaporated
13. customThe residue was purified by silica chromatography
14. washeluting with a gradient of ethyl acetate/methanol 9:1 up to ethyl acetate/methanol 8:2