Sodium Carbonate → 3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenol

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Reaction Steps

To a solution of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (550 mg, 1.68 mmol) and 4-tert-butylphenylboronic acid (345 mg, 2.52 mmol) in dioxane/H2O (20 mL/2 mL) was added Na2CO3 (356 mg, 3.36 mmol) followed by Pd(dba)2 (193 mg, 0.336 mmol) and X-Phos (80 mg, 0.168 mmol) under nitrogen with stirring. The mixture was refluxed for 16 h under nitrogen. After cooling, the solvent was concentrated in vacuo. The residue was purified by chromatography (silica, petroleum ether:EtOAc=3:1 to 1:1) to give 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenol (565 mg, 87%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.61 (s, 1H), 9.58 (s, 1H), 8.72 (s, 1H), 8.16 (s, 1H), 7.62 (s, 1H), 7.44-7.26 (m, 2H), 6.90-6.86 (m, 2H), 6.71 (d, 1H, J=7.8 Hz), 6.05 (d, 1H, J=8.1 Hz), 4.22-4.18 (m, 1H), 3.55-3.53 (m, 1H), 3.42-3.37 (m, 1H), 2.10-1.96 (m, 3H), 1.66 (brs, 1H), 1.13 (d, 3H, J=6.0 Hz). LC/MS: 387 [M+H]+; 385 [M−H]−, tR=1.72 min. HPLC: 95.63% at 214 nm, 95.18% at 254 nm, tR=2.72 min.

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