Potassium Phosphate, Tribasic → HCID 86685342, compound

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 3-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-(cyanomethyl)azetidine-1-carboxylate (Preparation N; 2.80 g, 6.76 mmol), 4-methoxybenzeneboronic acid (1.54 g, 10.1 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.644 g, 1.35 mmol) and K3PO4 (10.1 mL, 20.3 mmol) were suspended in 1,4-dioxane (30 mL) and purged with Ar (g). Pd2dba3 (0.619 g, 0.676 mmol) was added and the system sealed and heated at 75° C. overnight. The reaction mixture was diluted with EtOAc and saturated aqueous NaHCO3. The bi-phasic mixture was passed through a pad of Celite® to remove solids. The Celite® was washed with DCM and MeOH. The organic layer was separated and then washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford some crude material. This was combined with the DCM and MeOH washed off the Celite® to afford the crude total material. The crude material was suspended in DCM to load onto a column. Many solids did not dissolve and were collected and identified as desired crude material. The crude material was loaded onto a column and purified by flash column chromatography, eluting with 2-4% (9:1 MeOH:NH4OH)/DCM to provide tert-butyl 3-(cyanomethyl)-3-(4-(7-(4-methoxyphenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (3.42 g, 7.044 mmol, 104.3% yield). MS (apci) m/z=486.2 (M+H).

Provenance & Evidence