Potassium Phosphate, Tribasic → HCID 68358692, compound

Participants

Reaction Conditions

Reaction Steps

To a vial charged with a solution of phenylboronic acid (215 mg, 1.760 mmol), PdCl2(dppf)-CH2Cl2 adduct (47.9 mg, 0.059 mmol) and tert-butyl (((1S,3R)-3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)methyl)carbamate (290 mg, 0.587 mmol) in 1,4-dioxane (3.91 ml) was added a 2 M aqueous solution of potassium phosphate (880 μl, 1.760 mmol). The suspension was purged with nitrogen for 5 minutes. The vial was sealed and heated at 100° C. for 2 hrs. The reaction was diluted with methanol (10 ml), filtered, and concentrated, yielding a dark oil. The oil was taken up in ethyl acetate (50 ml). The solution was washed successively with water and brine. The ethyl acetate extract was dried with sodium sulfate, filtered, and concentrated under reduced pressure, yielding a dark oil. The oil was dissolved in 10% methanol-DCM (5 ml). The crude product mixture was loaded directly on a prepacked silica gel column. The crude product was purified via medium pressure chromatography (0-10% methanol-DCM solvent system over 25 minutes). The desired tert-butyl (((1S,3S)-3-((3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethyl-cyclopentyl)methyl)carbamate (236 mg, 0.480 mmol, 82% yield) was obtained as a white solid. ESI-MS m/z 492.4 ([M+H]+).

Provenance & Evidence