Reaktion #622928

Reaktionsgleichung

1-(aminomethyl)cyclopropanecarbonitrile

4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

DIEA

Na2CO3

→

1-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile

Ausbeute 66.0%

Lösungsmittel

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to room temperature
2. 2
   Sonstigepartitioned between EtOAc (10 mL) and water (20 mL)
3. 3
   SonstigeThe layers were separated
4. 4
   Waschenthe organic portion was sequentially washed with water (20 mL), brine (10 mL)
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe resulting residue was purified by flash chromatography on silica gel eluting with an EtOAc-heptane (0-50%) gradient

Vorschrift

A mixture of 1-(aminomethyl)cyclopropanecarbonitrile (0.67 g, 7.0 mmol), 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (2.01 g, 4.7 mmol), DIEA (1.64 ml, 9.35 mmol), Na2CO3 (0.99 g, 9.4 mmol) and NMP (2 mL) was heated at 110° C. for 25 hours. The reaction mixture was allowed to cool to room temperature and partitioned between EtOAc (10 mL) and water (20 mL). The layers were separated and the organic portion was sequentially washed with water (20 mL), brine (10 mL), and concentrated. The resulting residue was purified by flash chromatography on silica gel eluting with an EtOAc-heptane (0-50%) gradient to provide 1-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile (1.50 g, 3.06 mmol, 66%) as a white foam. LCMS (m/z) 491.1 (MH+), tR=0.99 minute.

Quelle