Reacción #999604

Ecuación de reacción

n-pentane ethyl acetate

3-(difluoromethyl)-1-methyl-pyrazole-4-carbonyl chloride

N-(1,3-thiazol-4-ylmethyl)-cyclopropylamine

triethylamine

→

N-cyclopropyl-N-(1,3-thiazol-4-yl-methyl)-1-methyl-3-difluoromethyl-pyrazole-4-carboxamide

Rendimiento 51.0%

Disolventes

tetrahydrofurane

tetrahydrofurane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroquenched with water
2. 2
   ExtracciónThe watery layer was extracted three times with ethyl acetate (3×20 ml)
3. 3
   Secadothe combined organic layers were dried over magnesium sulphate
4. 4
   Concentraciónconcentrated in vacuum

Procedimiento

20 ml (0.29 mol) of cyclopropylamine was added to a solution of 4.9 g (29.0 mmol) of 4-(chloromethyl)-thiazole hydrochloride in 45 ml ethanol and 45 ml of saturated aqueous sodium hydrogen carbonate. The reaction mixture was stirred for 20 hrs at ambient temperature and extracted with ethyl acetate (3×100 ml). The combined organic layers were dried over magnesium sulphate and concentrated in vacuum. Column chromatography (gradient n-pentane/ethyl acetate) yielded 1.5 g (32% yield) of N-(1,3-thiazol-4-ylmethyl)cyclopropylamine. At ambient temperature a solution of 0.28 g (1.4 mmol) of 3-(difluoromethyl)-1-methyl-pyrazole-4-carbonyl chloride in 2 ml of tetrahydrofurane was added drop wise to a solution of 0.20 g (1.3 mmol) of N-(1,3-thiazol-4-ylmethyl)-cyclopropylamine and 0.6 ml triethylamine in 4 ml tetrahydrofurane. The reaction mixture was stirred for 16 hrs at ambient temperature and quenched with water. The watery layer was extracted three times with ethyl acetate (3×20 ml), the combined organic layers were dried over magnesium sulphate and concentrated in vacuum. Column chromatography (gradient n-pentane/ethyl acetate) yielded 0.13 mg (51% yield) of N-cyclopropyl-N-(1,3-thiazol-4-yl-methyl)-1-methyl-3-difluoromethyl-pyrazole-4-carboxamide (M+1=313).

Fuente