Reaktion #679617

Reaktionsgleichung

1-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

tert-butyl 4-amino-1H-pyrazole-1-carboxylate

Cs2CO3

Xantphos

→

title compound 46

Ausbeute 12.0%

1-(2-(2-(2-((1H-Pyrazol-4-yl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Ausbeute 12.0%

Lösungsmittel

DCM

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas bubbled with N2 for 10 minutes
2. 2
   TemperaturThe reaction mixture was cooled to room temperature
3. 3
   Sonstigepurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 20-100% EtOAc in petroleum benzine 40-60° C.
4. 4
   Sonstige0-20% MeOH in EtOAc) to give a white solid
5. 5
   Sonstigeprecipitated by the addition of cyclohexane
6. 6
   SonstigeThe suspension was sonicated for 10 minutes
7. 7
   Sonstigethe precipitate was isolated by vacuum filtration
8. 8
   Waschenwashed with Et2O

Vorschrift

A mixture of 1-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A40 (0.147 g, 0.465 mmol), tert-butyl 4-amino-1H-pyrazole-1-carboxylate (0.102 g, 0.559 mmol), Cs2CO3 (0.455 g, 1.40 mmol), Xantphos (0.011 g, 0.019 mmol) and Pd(OAc)2 (0.002 g, 0.009 mmol) in 1,4-dioxane (5 mL) was bubbled with N2 for 10 minutes before being heated in the microwave for 20 minutes at 120° C. The reaction mixture was cooled to room temperature, adsorbed onto silica, and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 20-100% EtOAc in petroleum benzine 40-60° C., then 0-20% MeOH in EtOAc) to give a white solid. This solid was taken up in DCM and precipitated by the addition of cyclohexane. The suspension was sonicated for 10 minutes and the precipitate was isolated by vacuum filtration and washed with Et2O to give the title compound 46 as a white solid (0.021 g, 12%). LCMS-D: rt 2.98 min; m/z 363 [M+H]+.

Quelle