Sodium Carbonate → 3-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)-2-methylpropanenitrile

Temperature

90 °C

A solution of 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (2.5 g, 5.8 mmol), DIEA (2.0 mL, 11.6 mmol), and 3-amino-2-methylpropanenitrile (1.49 g, 17.7 mmol) in NMP (10 mL) was treated with Na2CO3 (1.23 g, 11.6 mmol) and the resulting reaction mixture heated at 90° C. overnight. The reaction was allowed to cool to room temperature and was partitioned between EtOAc (75 mL) and water (100 mL). The layers were separated and the organic portion was washed with saturated aqueous NaHCO3 solution (100 mL), brine (150 mL), dried (Na2SO4) and concentrated to a brown residue. Purification by flash chromatography (0-50% EtOAc-heptane) afforded 3-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)-2-methylpropanenitrile (2.79 g, 5.8 mmol) as a white solid: LCMS (m/z) 477.1 (MH+), tR=0.98 minute.

1. customthe resulting reaction mixture
2. temperatureto cool to room temperature
3. customwas partitioned between EtOAc (75 mL) and water (100 mL)
4. customThe layers were separated
5. washthe organic portion was washed with saturated aqueous NaHCO3 solution (100 mL), brine (150 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated to a brown residue
8. customPurification by flash chromatography (0-50% EtOAc-heptane)

ORD record

ord-c254d6222d65458789418a690f50cb21

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859548B2