反应详情

2M Trimethylaluminium (1.250 ml, 2.50 mmol) in toluene, was added dropwise to a stirred is solution of ethyl 5-(4-methylpiperazin-1-yl)thiophene-2-carboxylate (0.254 g, 1 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.247 g, 1.00 mmol) in toluene (7.14 ml) at 20° C. under nitrogen. The reaction mixture was stirred at ambient temperature for 16 h and then heated at 65° C. for 24 h. Ethyl acetate (5 mL) was added to the reaction mixture followed by a solution of potassium sodium tartrate (5 mL, 20% aqueous). More ethyl acetate (50 mL) and water (25 mL) was added and the mixture was filtered through celite. The filtrate was transferred to a separating funnel and the aqueous layer removed. The ethyl acetate layer was washed with saturated brine and then dried over magnesium sulphate. After filtration the solvent was evaporated to give the crude product as a yellow solid. The crude product was purified 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 (0.154 g, 33.8%) as a white solid.

1. customat 20° C.
2. temperatureheated at 65° C. for 24 h
3. filtrationthe mixture was filtered through celite
4. customThe filtrate was transferred to a separating funnel
5. customthe aqueous layer removed
6. washThe ethyl acetate layer was washed with saturated brine
7. dry with materialdried over magnesium sulphate
8. filtrationAfter filtration the solvent
9. customwas evaporated
10. customto give the crude product as a yellow solid
11. customThe crude product was purified by preparative HPLC
12. additionFractions containing the desired compound
13. customwere evaporated to dryness