Reaktion #972933

Reaktionsgleichung

Na2CO3

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

DIEA

3-aminopropionitrile

→

3-(4-(4-bromo-2-(1-methylcyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile

Ausbeute 100.0%

Lösungsmittel

EtOAc

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe resulting reaction mixture
2. 2
   Sonstigereaction
3. 3
   Temperaturto cool to room temperature
4. 4
   Waschenwas washed with water (100 mL), dilute aqueous NaHCO3 solution (100 mL), brine (150 mL)
5. 5
   Trocknendried (Na2SO4)
6. 6
   Einengenconcentrated
7. 7
   SonstigePurification of the resulting residue by flash chromatograhpy (SiO2, 0-50% EtOAc in heptane)

Vorschrift

Solid Na2CO3 (1.11 g, 10.5 mmol) was added to a solution of 4-(4-bromo-2-(1-methylcyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (I-3a, step 4, 2.33 g, 5.2 mmol), DIEA (1.8 mL, 10.5 mmol), and 3-aminopropionitrile (1.2 mL, 15.7 mmol) in NMP (3 mL) and the resulting reaction mixture was heated to 90° C. After 5 hours, LCMS indicated complete reaction and the reaction was allowed to cool to room temperature. EtOAc (75 mL) was added the organic phase was washed with water (100 mL), dilute aqueous NaHCO3 solution (100 mL), brine (150 mL), dried (Na2SO4), and concentrated. Purification of the resulting residue by flash chromatograhpy (SiO2, 0-50% EtOAc in heptane) provided 3-(4-(4-bromo-2-(1-methylcyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile (2.47 g, 5.2 mmol, 99% yield) as a foamy off-white solid: LCMS (m/z) 477.1 (MH+), tR=0.98 minute.

Quelle