1,2-Dimethoxyethane → 3-(4-(Aminomethyl)phenyl)-n-(tetrahydro-2h-pyran-4-yl)imidazo[1,2-b]pyridazin-6-amine

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Reaction Conditions

Reaction Steps

A mixture of 3-bromo-N-(tetrahydro-pyran-4-yl)imidazo[1,2-b]pyridazin-6-amine (100 mg, 0.34 mmol), 4-(aminomethyl)phenylboronic acid hydrochloride (160 mg, 0.84 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (25 mg, 0.034 mmol), potassium phosphate (360 mg, 1.7 mmol), DME (1.5 mL) and H2O (0.5 mL) was heated in a sealed conical vessel at 160° C. for 360 s by microwave irradiation. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 mL). The combined organic layers were concentrated under reduced pressure to afford an oil that was purified by reverse phase HPLC to afford [3-(4-aminomethyl-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(tetrahydro-pyran-4-yl)-amine (20.5 mg, 20%) as a yellow solid: 1H NMR (400 MHz, MeOD) δ 8.24 (d, J=8.4 Hz, 2H), 7.82 (s, 1H), 7.55 (d, J=8.4 Hz, 1H), 6.74 (d, J=10 Hz, 1H), 4.13 (s, 2H), 4.06-3.92 (m, 3H), 3.61 (t, J=11.2 Hz, 2H), 2.15 (d, J=12.8 Hz, 2H), 1.65 (qd, J=11.2, 4.4 Hz, 2H); LCMS (ESI) m/e 324.2 [(M+H)+, calcd for C18H22N5O 324.2].

Provenance & Evidence