Reaktion #92296

Reaktionsgleichung

DIEA

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

1-(trifluoromethyl)cyclopropanecarboxylic acid

HATU

→

final product

Ausbeute 64.5%

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

Ausbeute 64.5%

Lösungsmittel

DMF

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling in an ice bath for 10 minutes
2. 2
   Waschenwashed with water and brine (5 mL each)
3. 3
   Einengenconcentrated
4. 4
   Sonstigepurified by reverse-phase column chromatography
5. 5
   Wascheneluting with 5 to 72% acetonitrile/water

Vorschrift

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).

Quelle