N#N.Cl.Cl.[Br:5][C:6]1[N:10]2[N:11]=[C:12]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1.CCN(C(C)C)C(C)C.[N:30]([C:33]([CH3:36])([CH3:35])[CH3:34])=[C:31]=[O:32]>ClCCl>[Br:5][C:6]1[N:10]2[N:11]=[C:12]([N:15]3[CH2:16][CH2:17][N:18]([C:31]([NH:30][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[CH2:19][CH2:20]3)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1
To a rapidly stirred, 0° C., N2 blanketed, suspension of 3-bromo-6-piperazin-1-yl-imidazo[1,2-b]pyridazine dihydrochloride (934.9 mg, 2.6 mmol) and Hunig's base [7087-68-5] (1.8 mL, 10.6 mmol) in dichloromethane (26 mL) was added 2-isocyanato-2-methylpropane [1609-86-5] (340 μL, 2.9 mmol). The suspension was permitted to stir and warm to ambient temperature over 17 h and was then partitioned between brine and ethyl acetate. The organic phase was reduced in volume to precipitate product as 442.1 mg of yellow solid. A 129.3 mg aliquot was purified by preparative RP-HPLC to yield 61.8 mg of 4-(3-bromoimidazo[1,2-b]pyridazin-6-yl)-N-(tert-butyl)piperazine-1-carboxamide as a white powder, mp. 199-200° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28 (s, 8H) 2.51 (s, 1H) 3.30 (s, 1H) 3.39-3.46 (m, 4H) 3.48-3.54 (m, 4H) 7.26 (d, J=10.11 Hz, 1H) 7.61 (s, 1H) 7.88 (d, J=10.11 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ ppm 29.15, 43.05, 45.27, 49.94, 99.27, 110.77, 126.00, 131.50, 136.54, 155.16, 156.93. LRMS (ESI) m/z 381.1/383.1 [(M+H)]+, calc'd for C15H21BrN6O: 381.28.
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