反应详情

[(S)-1-(3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-methyl-carbamic acid isopropyl ester (120 mg, 0.3 mmol), 5-fluoro-2-methoxy phenyl boronic acid (107 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, then purified on shimadzu neutral phase prep and product fractions lyophilized to get 52 mg (S)-isopropyl(1-(3-(5-fluoro-2-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)(methyl)carbamate. 1H NMR (400 MHz, DMSO-d6) δ 8.33-8.38 (m, 1H), 7.99 (s, 1H), 7.91 (d, J=9.85 Hz, 1H), 7.13-7.18 (m, 2H), 6.92 (d, J=9.85 Hz, 1H), 4.76-4.86 (m, 2H), 3.87 (s, 3H), 3.63-3.70 (m, 2H), 3.36-3.50 (m, 2H), 2.80 (s, 3H), 2.10-2.22 (m, 2H), 1.21 (d, J=6.32 Hz, 6H). (ESI) m/z 428 [(M+H)]+, calc'd for C22H26FN5O3: 427.4.

1. customReaction
2. filtrationwas then filtered through celite with acetonitrile
3. custompurified on shimadzu neutral phase prep and product fractions