Reacción #61515

Ecuación de reacción

4-cyano-5-propyl-2H-pyrazole-3-carboxylic acid ethyl ester

sodium hydride

NaOH

3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole

→

2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-propyl-2H-pyrazole-3-carboxylic acid

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas cooled to −70° C.
2. 2
   workup.STIRRINGThe reaction was stirred at room temperature for 3 h
3. 3
   OtroThe product was purified by preparative RP-HPLC
4. 4
   Lavadoeluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid)
5. 5
   OtroAfter lyophilization the product was obtained as a white solid

Procedimiento

112 mg (0.5 mmol) of 4-cyano-5-propyl-2H-pyrazole-3-carboxylic acid ethyl ester was dissolved in 2 ml of DMF and 23.8 mg (0.6 mmol) of sodium hydride (60% in mineral oil) were added at RT. After stirring for 20 min at room temperature the solution was cooled to −70° C. and 166 mg (0.6 mmol) of 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added. The reaction was stirred at room temperature for 3 h. The reaction solution was treated with 1 ml of 2N aqueous NaOH for 16h at room temperature. The product was purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). After lyophilization the product was obtained as a white solid.

Fuente