Water → (S)-isopropyl (1-(3-(2-methoxy-5-methylpyridin-3-yl)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)(methyl)carbamate

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Reaction Steps

[(S)-1-(3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-methyl-carbamic acid isopropyl ester (120 mg, 0.3 mmol), 2-methoxy-5-methylpyridine-3-boronic acid (105 mg, 0.6 mmol), potassium carbonate (65 mg, 0.45 mmol), and Pd(dppf)Cl2 dichloromethane (26 mg, 0.03 mmol) were taken up in 2 mL acetonitrile and 1 mL water and microwaved in a sealed tube at 140° C. for 15 minutes. Reaction was then filtered through celite with acetonitrile reduced in vacuo, the purified on shimadzu neutral phase prep and product fractions lyophilized to afford 65 mg (S)-isopropyl(1-(3-(2-methoxy-5-methylpyridin-3-yl)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)(methyl)carbamate. 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J=2.02 Hz, 1H), 7.99 (s, 1H), 7.94-7.97 (m, 1H), 7.91 (d, J=9.60 Hz, 1H), 6.92 (d, J=9.85 Hz, 1H), 4.75-4.85 (m, 2H), 3.95 (s, 3H), 3.64-3.70 (m, 2H), 3.38-3.51 (m, 2H), 2.81 (s, 3H), 2.29 (s, 3H), 2.11-2.23 (m, 2H), 1.21 (d, J=6.32 Hz, 6H). (ESI) m/z 425 [(M+H)]+, calc'd for C22H28N6O3: 424.5.

Provenance & Evidence