Reaktion #45141

Reaktionsgleichung

trimethylaluminium

ethyl 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)benzoate

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

→

title compound

Ausbeute 33.7%

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

Ausbeute 33.7%

Lösungsmittel

toluene

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled
2. 2
   Sonstigequenched with methanol (15 ml) and 2N hydrochloric acid (5 ml)
3. 3
   SonstigeThe crude reaction mixture
4. 4
   Sonstigewas purified by ion exchange chromatography on a SCX column
5. 5
   Wascheneluting with 7N ammonia in methanol
6. 6
   SonstigeThe appropriate fractions were evaporated
7. 7
   Sonstigeto give an oil
8. 8
   SonstigeThe crude product was purified by silica column chromatography
9. 9
   Wascheneluting with a gradient of 0 to 10% 2.5N ammonia/MeOH in DCM
10. 10
    SonstigePure fractions were evaporated to dryness
11. 11
    Sonstigeto afford, on crystallisation from DCM/diethyl ether

Vorschrift

A 2M solution of trimethylaluminium (2.500 mL, 5.00 mmol) in toluene, was added dropwise to a stirred suspension of ethyl 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)benzoate (0.643 g, 2 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.495 g, 2.00 mmol) in toluene (10 mL) at room temperature. The solution was then heated at 60° C. for 18 h. The reaction mixture was cooled and quenched with methanol (15 ml) and 2N hydrochloric acid (5 ml). The crude reaction mixture was purified by ion exchange chromatography on a SCX column, eluting with 7N ammonia in methanol. The appropriate fractions were evaporated to give an oil. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 10% 2.5N ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford, on crystallisation from DCM/diethyl ether, the title compound (0.322 g, 33.7%) as a cream solid.

Quelle