Reaktion #45076

Reaktionsgleichung

Methyl 4-(1-cyclopropylpiperidin-4-yl)benzoate

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

trimethylaluminium

→

title compound

Ausbeute 35.8%

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

Ausbeute 35.8%

Lösungsmittel

—

toluene,under nitrogen

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled
2. 2
   Sonstigethe reaction quenched with methanol (40 ml)
3. 3
   SonstigeThe crude reaction mixture
4. 4
   Sonstigewas purified by ion exchange chromatography
5. 5
   WaschenThe crude product was eluted from the column
6. 6
   Sonstigewere evaporated to dryness
7. 7
   SonstigeThe crude product was purified by silica column chromatography
8. 8
   Wascheneluting with a gradient of 0 to 5% 2.5M ammonia/methanol in DCM
9. 9
   SonstigePure fractions were evaporated to dryness
10. 10
    Sonstigethe product crystallised from DCM/diethyl ether

Vorschrift

Methyl 4-(1-cyclopropylpiperidin-4-yl)benzoate (0.259 g, 1 mmol), 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.247 g, 1.00 mmol) in toluene (10 ml) was treated with a 2M solution of trimethylaluminium (1.250 ml, 2.50 mmol) in toluene,under nitrogen. The reaction mixture was heated at 60° C. for 18 h. The reaction mixture was cooled and the reaction quenched with methanol (40 ml) and acidified with 2N HCl (1 ml). The crude reaction mixture was purified by ion exchange chromatography, using an SCX column. The crude product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% 2.5M ammonia/methanol in DCM. Pure fractions were evaporated to dryness and the product crystallised from DCM/diethyl ether to give the title compound (0.170 g, 35.8%) as a white solid.

Quelle