3,6-Dibromopyridazine → HCID 86686650, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 3,6-dibromo-pyridazine (400 mg, 1.68 mmol) in 8 mL Toluene in a dry pressure tube were added 4-oxo-3,9-diaza-bicyclo[4.2.1]nonane-9-carbo-xylic acid tert-butyl ester (323 mg, 1.345 mmol), Pd2(dba)3 (154 mg, 0.168 mmol), xantphos (195 mg, 0.336 mmol) and NaOt-Bu (242 mg, 2.52 mmol) and the suspension was bubbled with N2 for 3 min. Then the tube was sealed and the mixture was heated for 3 h at 100° C. Then the seal was open and the mixture was added with more of Pd2(dba)3 (41 mg, 0.045 mmol), xantphos (52 mg, 0.091 mmol), NaOt-Bu (65 mg, 0.680 mmol) and 2-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (124 mg, 0.453 mmol). The mixture was again heated at 100 C for 16 h and the suspension was filtered through a celite plug and washed with 10% MeOH in DCM. The collective filtrates were combined and purified by two consecutive SiO2 columns to give 3-[6-(7-cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)pyridazin-3-yl]-4-oxo-3,9-diaza-bicyclo[4.2.1]nonane-9-carboxylic acid tert-butyl ester (66 mg, 0.112 mmol, 8% yield) as a white solid. MS m/z 590.6 (M+H)+.

Provenance & Evidence