Reacción #45124

Ecuación de reacción

Trimethylaluminium

methyl 2-(4-ethyl-3-methylpiperazin-1-yl)pyrimidine-5-carboxylate

5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine

→

title compound

Rendimiento 49.0%

N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-2-(4-ethyl-3-methylpiperazin-1-yl)pyrimidine-5-carboxamide

Rendimiento 49.0%

Disolventes

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction mixture was quenched into methanol (100 mL)
2. 2
   workup.ADDITIONtreated with HCl (2N aqueous solution
3. 3
   OtroThe crude product was purified by ion exchange chromatography
4. 4
   LavadoThe desired product was eluted from the column
5. 5
   Otrowere evaporated to dryness
6. 6
   Otroto afford impure product as a yellow dry film
7. 7
   OtroThe crude product was purified by preparative HPLC
8. 8
   workup.ADDITIONFractions containing the desired compound
9. 9
   Otrowere evaporated to dryness

Procedimiento

Trimethylaluminium (2M in toluene, 1.65 ml, 3.31 mmol) was added dropwise to a stirred suspension of methyl 2-(4-ethyl-3-methylpiperazin-1-yl)pyrimidine-5-carboxylate (303 mg, 1.15 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (283 mg, 1.15 mmol) in toluene (5.73 ml) at room temperature. The resulting solution was stirred at 60° C. overnight. The reaction mixture was quenched into methanol (100 mL) and treated with HCl (2N aqueous solution, until the pH was 7 or lower). The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford impure product as a yellow dry film. 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 (269 mg, 49%) as a cream solid.

Fuente