Nitrogen → HCID 57955356, compound

Participants

Reaction Steps

To a flask charged with N2 was added 1-{4-[4-amino-7-bromo-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea (Intermediate AAC, Step 1) (500 mg, 0.875 mmol, 1.0 eq) and tert-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (677 mg, 2.19 mmol, 2.5 eq) followed by 1,4-dioxane (5 mL). Nitrogen was bubbled through the solution for 15 min and then 2M Na2CO3 (6 eq) was added. Nitrogen again bubbled through solution for 15 minutes and [1,1′-Bis(diphenylphosphino)ferrocene] (143 mg, 0.2 eq) was added. N2 was bubbled through the solution for an additional 15 min and then the reaction was placed in a preheated 80° C. oil bath for 17 h. The reaction solution was allowed to cool to rt and was diluted with EtOAc and water. The organic layer was washed water and brine. The combined organic layers were dried (Na2SO4), filtered, condensed, and purified via flash column chromatography (1:1 tetrahydrofuran/hexanes). The purified fractions were collected, evaporated, and left under vacuum overnight to yield the title compound (520 mg, 88.2% yield). 1H-NMR (DMSO-d6) MS [M+H]+=674; LCMS RT=3.51 min.

Provenance & Evidence