反应详情

温度

60 °C

Trimethylaluminium (2M in toluene, 1.31 ml, 2.62 mmol) was added dropwise to a suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (260 mg, 1.05 mmol) and methyl 2-(3,4-dimethylpiperazin-1-yl)pyrimidine-5-carboxylate (263 mg, 1.05 mmol) in toluene (5.26 ml) at 25° C. The resulting solution was stirred at 60° C. for 18 h. The reaction mixture was poured into methanol (50 mL) and acidified with HCl (2M aqueous solution, to obtain a clear freely stirring solution). The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford impure product. The impure material was purified by silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane. Fractions containing product were evaporated to dryness to give material that was still impure. The residue was repurified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (175 mg, 36%) as a white solid.

1. customto obtain a clear freely stirring solution)
2. customThe crude product was purified by ion exchange chromatography
3. washThe desired product was eluted from the column
4. customevaporated to dryness
5. customto afford impure product
6. customThe impure material was purified by silica column chromatography
7. washeluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane
8. additionFractions containing product
9. customwere evaporated to dryness
10. customto give material that
11. customThe residue was repurified by preparative HPLC
12. additionFractions containing the desired compound
13. customwere evaporated to dryness