1,2-Dimethoxyethane → 3-cyclopropyl-3-(4-(7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

Participants

Reaction Conditions

Reaction Steps

A flask was charged with 5-chloro-7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Step C, 150 mg, 0.429 mmol), 3-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile (Preparation P; 185 mg, 0.643 mmol) and K3PO4 (273 mg, 1.29 mmol). DME (2.5 mL) and H2O (1.5 mL) were added and the resulting solution was purged with N2 for 15 minutes. Pd(PPh3)4 (49.5 mg, 0.0429 mmol) was added, the flask sealed, and the mixture stirred at 80° C. for 3.5 hours. The mixture was cooled to ambient temperature and was diluted with H2O (5 mL). The mixture was extracted with 50% EtOAc/hexanes and the combined extracts were washed with saturated NaCl and dried over MgSO4/activated carbon. The dried solution was eluted through a SiO2 column eluting with 50% EtOAc/hexanes, EtOAc and 10% MeOH/EtOAc. The EtOAc and 10% MeOH/EtOAc pools were combined and concentrated to give a gold syrup. The syrup was dissolved in Et2O and concentrated to give the title compound (153 mg, 75.0% yield) as a brittle, light beige foam. MS (apci) m/z=475.3 (M+H).

Provenance & Evidence