Dichloromethane → 5-(6-(2-(2,5-Dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile

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Reaction Steps

In step 4-2, sodium carbonate (30 mg, 0.30 mmol), 3-cyano-4-fluoro phenylboronic acid (30 mg, 0.24 mmol) and Pd(DPPF)-dichloride catalyst (1,1′ bis(diphenylsphosphino-ferrocene)-dichloropalladium (II) adduct with dichloromethane) (10 mg, 0.012 mmol) was added into in a microwave vessel containing a solution of 3-bromo-6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (50 mg, 0.13 mmol) and 2.5 mL of 1,4-dioxane/water (3:1). The reaction mixture was subjected to the following microwave conditions using a laboratory microwave instrument (conditions: 150° C., 200 W max threshold, 20 atm. Max pressure, 20 minute reaction time). The resulting solution was purified using preparatory LC/MS (reverse phase C-18 chromatography) to yield 5-(6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile (4-2). 1H NMR (400 MHz, D3 acetonitrile) δ ppm 8.50-8.10 (m, 2H), 7.80 (br s, 1H), 7.50 (app d, J=8.5 Hz, 1H), 7.20 (app t, J=6.5 Hz, 1H), 7.06 (d, J=6.5 Hz, 1H), 6.93 (d, J=6.6 Hz, 1H), 6.81 (br s, 1H), 6.60 (br s, 1H), 5.22 (app dd, J=6.2, 2.1 Hz, 1H), 4.05-4.00 (m, 1H), 3.76 (app q, J=6.4 Hz, 1H), 3.36 (app d, J=2.2 Hz, 1H), 2.58-2.43 (m, 1H), 2.24 (br s, 6H), 2.19-2.08 (m, 2H). LCMS observed m/z 412.2.

Provenance & Evidence