Water → 6-bromo-4-(((2R,3R)-1,3-dihydroxybutan-2-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

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Reaction Conditions

Reaction Steps

A mixture of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (686 mg, 2.5 mmol), (2R,3R)-2-aminobutane-1,3-diol (394 mg, 3.75 mmol) and diisopropylethylamine (0.873 mL, 5.00 mmol) in DMA (10 mL) was heated to 125° C. for 3 hr. After cooling to rt, the volatiles were removed under high vacuum to afford a red oil that was treated with ˜25 ml of water. A gummy solid formed and the mixture was stirred at rt overnight. A few crystals of pure title compound from a previous batch were added at the beginning of the stirring. The suspension was filtered and dried to afford a yellow solid that was washed with 25 ml of Et2O:EtOAc, 1:1. Drying afforded 6-bromo-4-(((2R,3R)-1,3-dihydroxybutan-2-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (670 mg, 1.952 mmol, 78% yield) as a pale yellow solid. 1H NMR (400 MHz, CD3OD) δ 8.13 (s, 1H), 7.62 (d, J=1.8 Hz, 1H), 7.09 (d, J=1.5 Hz, 1H), 4.21 (dd, J=6.4, 2.6 Hz, 1H), 4.15-4.06 (m, 1H), 3.90-3.74 (m, 2H), 1.23 (d, J=6.4 Hz, 3H); (ES+) m/z: 343.1, 345.1 (M+H); LC retention time: 1.957 min (analytical HPLC Method P).

Provenance & Evidence