Potassium Phosphate, Tribasic → HCID 68291887, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(((2R,3R)-3-(benzyloxy)-1-hydroxybutan-2-yl)amino)-6-bromopyrrolo[1,2-b]pyridazine-3-carboxamide (2.98 g, 6.88 mmol), phenylboronic acid (1.677 g, 13.75 mmol), palladium (II) acetate (0.309 g, 1.375 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbyphenyl (1.311 g, 2.75 mmol) and potassium phosphate, tribasic, 2M (20.63 mL, 41.3 mmol) in dioxane (50 mL) was heated to 100° C. for 1 hr. After cooling to rt, the reaction mixture was filtered through a celite and the filtrate was partitioned between EtOAc (200 ml) and water (200 ml). The organic layer was washed with brine (150 ml), dried (MgSO4) and concentrated to afford a brown solid that was triturated with ether. Filtration and drying afforded 4-(((2R,3R)-3-(benzyloxy)-1-hydroxybutan-2-yl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide (2.17 g, 5.04 mmol, 73.3% yield) as a tan solid. 1H NMR (400 MHz, CD3OD) δ 8.16-8.11 (m, 1H), 7.94 (d, J=1.8 Hz, 1H), 7.73-7.67 (m, 2H), 7.45-7.21 (m, 9H), 4.76 (d, J=11.9 Hz, 1H), 4.56 (d, J=11.9 Hz, 1H), 4.44-4.33 (m, 1H), 4.09 (qd, J=6.3, 2.8 Hz, 1H), 3.96-3.83 (m, 2H), 1.31 (d, J=6.4 Hz, 3H). MS (ES+) m/z: 431.1 (M+H); LC retention time: 2.858 min (analytical HPLC Method B).

Provenance & Evidence