Reaktion #45021

Reaktionsgleichung

5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]thiophene-2-carboxylic acid

1-chloro-N,N,2-trimethyl-prop-1-en-1-amine

HCl

dioxane

Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate

→

title compound

Ausbeute 13.5%

N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-5-piperazin-1-yl-thiophene-2-carboxamide

Ausbeute 13.5%

Lösungsmittel

THF

pyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction was heated to 65° C. for 18 h
2. 2
   TemperaturThe reaction mixture was then cooled to room temperature
3. 3
   workup.STIRRINGThe mixture was stirred overnight at room temperature
4. 4
   Sonstigeevaporated
5. 5
   Sonstigethe residue was purified by acidic prep
6. 6
   WaschenHPLC, eluting with a gradient of 24-32% MeCN in 0.1% TFA in water
7. 7
   Sonstigeevaporated

Vorschrift

5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]thiophene-2-carboxylic acid (150 mg, mmol) was dissolved in dry THF (10 ml) under nitrogen, 1-chloro-N,N,2-trimethyl-prop-1-en-1-amine (177 μl, mmol) was added and the mixture was stirred at room temperature for 3.5 h. Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate (167 mg, mmol) and pyridine (47 μl, mmol) were added and the reaction was heated to 65° C. for 18 h. The reaction mixture was then cooled to room temperature and 4M HCl in dioxane (2.0 ml, 2.0 mmol) added. The mixture was stirred overnight at room temperature, evaporated and the residue was purified by acidic prep. HPLC, eluting with a gradient of 24-32% MeCN in 0.1% TFA in water. The clean fractions were taken and evaporated to give the title compound as a pale green solid (28.7 mg, 11%); 1H NMR (399.902 MHz, DMSO) δ 2.79 (s, 4H), 3.21 (s, 4H), 3.34 (s, 4H), 3.64 (s, 6H), 6.29 (m, 5H), 7.77 (m, 1H), 8.71 (s, 1H), 10.37 (s, 1H) MS: m/z=442 (MH+)

Quelle