Reaktion #45115

Reaktionsgleichung

HCl

Trimethylaluminium

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

methyl 2-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)pyrimidine-5-carboxylate

→

title compound

Ausbeute 39.4%

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

Ausbeute 39.4%

Lösungsmittel

methanol

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto obtain a clear freely stirring solution)
2. 2
   SonstigeThe crude product was purified by ion exchange chromatography
3. 3
   WaschenThe desired product was eluted from the column
4. 4
   Sonstigeevaporated to dryness
5. 5
   Sonstigeto afford impure product
6. 6
   SonstigeThe impure material was purified by preparative HPLC
7. 7
   workup.ADDITIONFractions containing the desired compound
8. 8
   Sonstigewere evaporated to dryness

Vorschrift

Trimethylaluminium (2M in toluene, 1.04 ml, 2.08 mmol) was added dropwise to a suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (205 mg, 0.83 mmol) and methyl 2-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)pyrimidine-5-carboxylate (220 mg, 0.83 mmol) in toluene (5.257 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 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 (157 mg, 39%) as a white solid.

Quelle