Potassium Phosphate, Tribasic → (+/-)-(cis)-Benzyl 3-(3-carbamoyl-6-(6-methoxypyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-ylamino)-4-methylpyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of (+/−)-(cis)-benzyl 3-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-4-methylpyrrolidine-1-carboxylate (0.40 g, 0.847 mmol), (6-methoxypyridin-3-yl)boronic acid (0.168 g, 1.10 mmol), palladium acetate (9.51 mg, 0.042 mmol) and 2-(Dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.040 g, 0.085 mmol) in dioxane (3.0 mL) was degassed by purging with argon for 3 min. Aqueous potassium phosphate (2.0 M) (1.27 mL, 2.54 mmol) was added and purging with argon was continued for 2 min. The reaction vial was sealed and heated at 95° C. for 3 h then the resulting mixture was cooled and concentrated to remove dioxane and the residue was taken up in EtOAc (300 mL). The resulting solution was washed with water, brine and dried over MgSO4, filtered and concentrated to afford a yellow solid as the crude product mixture. This material was purified by preparative chromatography using CH2Cl2/MeOH mixtures as the eluant and a 40 g silica cartridge. Fractions containing the major product were combined and concentrated to afford a bright yellow solid as the title compound. HPLC (method B) retntion time=3.65 min. LCMS (m+1)=501.3.

Provenance & Evidence