反应详情

2M Trimethylaluminium (1.250 ml, 2.50 mmol) in toluene, was added dropwise to a stirred solution of ethyl 5-(4-methylpiperazin-1-yl)thiophene-2-carboxylate (0.254 g, 1 mmol) and 5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine hydrochloride (0.286 g, 1.00 mmol) in toluene (7.14 ml) at 20° C. under nitrogen. The reaction mixture was stirred at room temperature for 18 h and then heated at 65° C. for 6 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. 147 g, 32.1%) as a white solid.

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