1,2-Dimethoxyethane → 6-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (160 mg, 0.61 mmol), (1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)boronic acid (200 mg, 0.73 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (50 mg, 0.06 mmol), potassium phosphate (250 mg, 1.2 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 6-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one (90 mg, 44%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.11-8.20 (m, 2H), 7.94 (d, J=8.2 Hz, 1H), 7.84 (s, 1H), 7.57 (d, J=9.7 Hz, 1H), 6.67 (d, J=9.7 Hz, 1H), 3.50 (t, J=6.7 Hz, 2H), 3.34 (t, J=7.2 Hz, 2H), 3.00 (t, J=6.6 Hz, 2H), 1.60-1.75 (m, 2H), 1.36-1.50 (m, 2H), 0.95 (t, J=7.4 Hz, 3H); LCMS (ESI) m/e 336.2 [(M+H)+, calcd for C19H22N6O 336.2].

Provenance & Evidence