Reacción #992701

Ecuación de reacción

2-amino-3-methyl-N-(1-methylethyl)-benzeneacetamide

title product

2-amino-3-methyl-N-(1-methylethyl)benzeneacetamide

N,N-diisopropyl-ethylamine

1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

oxalyl chloride

→

title compound

1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[2-[(1-methylethyl)amino]-2-oxoethyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Disolventes

tetrahydrofuran

dichloromethane

Dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroresulting in a solution
2. 2
   OtroThe volatiles were removed with a rotary evaporator
3. 3
   workup.DISSOLUTIONThe residue was dissolved in 10 mL of tetrahydrofuran
4. 4
   workup.STIRRINGThe reaction mixture was stirred overnight at room temperature
5. 5
   Lavadothe mixture was washed with water
6. 6
   Secadodried (sodium sulfate)
7. 7
   OtroThe solvent was removed with a rotary evaporator
8. 8
   OtroThe residue was purified by MPLC (40→60% ethyl acetate in hexanes as eluant)

Procedimiento

To a slurry of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (for preparation see WO 02/48115, 0.19 g, 0.66 mmol) in 10 mL of dichloromethane was added oxalyl chloride (0.087 mL, 1.0 mmol) and two drops of N,N-dimethylformamide. The reaction mixture was stirred for 15 minutes, resulting in a solution. The volatiles were removed with a rotary evaporator. The residue was dissolved in 10 mL of tetrahydrofuran, and the solution was added dropwise at 0° C. to 2-amino-3-methyl-N-(1-methylethyl)-benzeneacetamide (i.e. the title product of Step B) (0.14 g, 0.66 mmol), N,N-diisopropyl-ethylamine, (0.23 mL, 1.3 mmol) and 4-(dimethylamino)pyridine (5 mg) in 5 mL of tetrahydrofuran. The reaction mixture was stirred overnight at room temperature. Dichloromethane was added and the mixture was washed with water and dried (sodium sulfate). The solvent was removed with a rotary evaporator. The residue was purified by MPLC (40→60% ethyl acetate in hexanes as eluant) to afford the title compound plus an impurity. The material was purified further by MPLC (20→30% ethyl acetate in 1-chlorobutane as eluant) to afford the title product, a compound of the present invention, as a white solid (0.12 g), m.p. 206-207° C.

Fuente