Reacción #92296

Ecuación de reacción

DIEA

(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

1-(trifluoromethyl)cyclopropanecarboxylic acid

HATU

→

final product

Rendimiento 64.5%

(R)—N-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-1-(trifluoromethyl)cyclopropanecarboxamide

Rendimiento 64.5%

Disolventes

DMF

EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling in an ice bath for 10 minutes
2. 2
   Lavadowashed with water and brine (5 mL each)
3. 3
   Concentraciónconcentrated
4. 4
   Otropurified by reverse-phase column chromatography
5. 5
   Lavadoeluting with 5 to 72% acetonitrile/water

Procedimiento

To a mixture of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 25 mg, 0.079 mmol), 1-(trifluoromethyl)cyclopropanecarboxylic acid (15 mg, 0.095 mmol), and HATU (36 mg, 0.095 mmol) was added 0.6 mL DMF to make a solution. After cooling in an ice bath for 10 minutes, DIEA (0.041 mL, 0.24 mmol) was added to the reaction drop-wise. The reaction was allowed to warm up to ambient temperature and stirred overnight. The reaction mixture was diluted with EtOAc (15 mL), washed with water and brine (5 mL each), concentrated, and purified by reverse-phase column chromatography, eluting with 5 to 72% acetonitrile/water to yield the final product as a beige solid (23 mg, 63% yield). MS (apci) m/z=452.2 (M+H).

Fuente