反应详情

温度

60 °C

Trimethylaluminium (1.25 ml, 2.50 mmol) was added dropwise to a stirred suspension of methyl 2-(4-ethyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylate (265 mg, 1.00 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (248 mg, 1.00 mmol) in toluene (5.01 ml) at 25° C. The resulting solution was stirred at 60° C. for 18 h. The cooled reaction mixture was quenched into methanol (50 mL) and treated with HCl (2M aqueous solution, to pH7 or lower) and 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 crude product was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing desired product still contained an impurity, so they were concentrated to dryness and purified by crystallisation from MeCN to afford the title compound (104 mg, 22%) as a cream solid.

1. customThe cooled reaction mixture
2. customwas quenched into methanol (50 mL)
3. additiontreated with HCl (2M aqueous solution, to pH7 or lower)
4. custompurified by ion exchange chromatography
5. washThe desired product was eluted from the column
6. customevaporated to dryness
7. customto afford impure product
8. customThe crude product was purified by preparative HPLC
9. additionFractions containing desired product
10. concentrationso they were concentrated to dryness
11. custompurified by crystallisation from MeCN