Reacción #1857584

Ecuación de reacción

[3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid

oxalyl chloride

sodium hydrogencarbonate

4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride

triethylamine

→

2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone

Disolventes

dichloromethane

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solvent and the excess reagent are removed under reduced pressure
2. 2
   workup.DISSOLUTIONThe solid residue is again dissolved in dichloromethane and, at 0° C.
3. 3
   workup.STIRRINGThe reaction mixture is stirred at room temperature overnight
4. 4
   Otrothe aqueous phase is removed
5. 5
   Extracciónextracted with ethyl acetate
6. 6
   SecadoThe combined organic phases are dried over sodium sulphate
7. 7
   Concentraciónconcentrated
8. 8
   OtroPurification by column chromatography

Procedimiento

To a solution of [3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid (177 mg) in dichloromethane (40 ml) are added, at 0° C., oxalyl chloride (290 mg) and one drop of N,N-dimethylformamide. The reaction mixture is stirred at room temperature for 2 hours. The solvent and the excess reagent are removed under reduced pressure. The solid residue is again dissolved in dichloromethane and, at 0° C., added dropwise to a solution of 4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride and triethylamine (5.0 eq.) in dichloromethane (25 ml). The reaction mixture is stirred at room temperature overnight. Then it is admixed with concentrated sodium hydrogencarbonate solution, and the aqueous phase is removed and extracted with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated. Purification by column chromatography gives 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (110 mg).

Fuente