To a mixture of 4-(3-bromoimidazo[1,2-b]pyridazin-6-yl)-N-isopropylpiperazine-1-carboxamide (481.5 mg, 1.3 mmol), phenyl boronic acid [98-80-8] (191.8 mg, 1.6 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (608.4 mg, 2.6 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (111.4 mg, 0.1 mmol) contained in a 50 mL round bottomed flask was added a solution of 30% (v/v) water in 1,2-dimethoxyethane (25 mL) and a magnetic stir bar. The reaction pot was fitted to a reflux condenser, lowered into an ambient temperature oil bath, and the system taken through 10 evacuation/N2 blanket cycles while being rapidly stirred. The rapidly stirred, N2 blanketed, reaction was heated to an oil bath temperature of 85° C. for 17 h then cooled and partitioned between brine (pH adjusted to 10 with 3N aqueous sodium hydroxide) and ethyl acetate. The phase separated extract was dried (MgSO4) and evaporated to afford a brown oil which was purified by preparative RP-HPLC. Isolated product was dissolved in methanol, diluted with concentrated hydrochloric acid, evaporated to dryness, redissolved in methanol and precipitated by the addition of diethyl ether. Filtration of the precipitate yielded 219.4 mg of N-isopropyl-4-(3-phenylimidazo[1,2-b]pyridazin-6-yl)piperazine-1-carboxamide monohydrochloride salt as a white powder, mp. 217-218° C. (dec). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.08 (d, J=6.57 Hz, 6H) 2.51 (d, J=1.52 Hz, 2H) 3.50 (d, J=5.05 Hz, 4H) 3.56-3.63 (m, 4H) 3.73-3.82 (m, 1H) 7.49 (d, J=7.33 Hz, 1H) 7.54-7.60 (m, 2H) 7.80 (d, J=10.10 Hz, 1H) 8.08-8.13 (m, 2H) 8.22 (d, J=10.11 Hz, 1H) 8.53 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ ppm 22.88, 41.82, 42.69, 45.13, 116.22, 120.96, 122.08, 126.38, 127.20, 128.03, 128.76, 129.02, 132.77, 155.89, 156.69. LRMS (ESI) m/z 365.1 [(M+H)]+, calc'd for C20H24N6O: 364.45. mw=364.45.
