Phosphorus oxychloride → 5-chloro-7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

Participants

Reaction Steps

To a solution of 7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5(6H)-one (Step B, 772 mg, 2.33 mmol) in dry DCM (15 mL) was added DIEA (1.22 mL, 6.99 mmol) and the mixture was stirred at ambient temperature for 5 minutes. The mixture was cooled to 0° C. and POCl3 (855 μL, 9.32 mmol) was added. The mixture was stirred for 1 hour at 0° C. then at ambient temperature for 18 hours. The reaction mixture was concentrated and the residual syrup was dissolved in EtOAc (15 mL). The solution was added dropwise to stirred 1M K2CO3 (20 mL) cooled to 0° C. and stirred for 30 minutes. The mixture was allowed to reach ambient temperature and the EtOAc layer was removed. The remaining aqueous layer was extracted with EtOAc (2×) and the combined EtOAc fractions were washed with saturated NaCl. The EtOAc solution was dried over MgSO4/activated carbon, filtered through a packed Celite plug (EtOAc elution) and concentrated. The residual dark syrup was dissolved in Et2O, treated with activated carbon and filtered through a packed Celite pug (Et2O elution). The Et2O solution was concentrated to give a brittle tan foam that was pulverized to a flowing solid and dried in vacuum. This afforded the title compound (416 mg, 51.0% yield) as a light tan solid. MS (apci) m/z=350.1 (M+H).

Provenance & Evidence