1,4-Dioxane → HCID 46175032, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(6-((6-bromo-1H-benzo[d][1,2,3]triazol-1-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)-N-(cyclopropanecarbonyl)cyclopropanecarboxamide 13E (0.7 g, 1.457 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.303 g, 1.457 mmol) and PdCl2(dppf)-CH2Cl2 (0.06 g, 0.075 mmol) in Na2CO3 (2N, 6 mL)/dioxane (12 mL) was heated in a microwave at 110° C. for 45 min. The reaction was filtered and rinsed with EtOAc. This reaction was repeated twice. The organic solutions were combined and washed with 5% citric acid followed by NaHCO3, dried with MgSO4, and filtered. MeOH was added to the EtOAc solution to give 5% MeOH (v/v), and the resulting solution was filtered through a short silica column and rinsed thoroughly with 5% MeOH/EtOAc. Activated charcoal (1 g) was added to the eluent and stirred at ambient temperature for 1 hr. The solution was filtered through Celite and concentrated to dryness via rotary evaporation. The resulting material was suspended in EtOAc (50 mL) and sonicated. The resulting solid was collected by filtration and rinsed with EtOAc to provide the title compound, N-(6-((6-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d][1,2,3]triazol-1-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide 13 (820 mg, 1.98 mmol, 45%). The filtrate was concentrated and reconstituted in 10% MeOH/EtOAc, loaded on a short silica column and eluted with 10% MeOH/EA to give provide additional product (190 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.76-0.86 (m, 4 H) 1.88-1.97 (m, 1 H) 3.88 (s, 3H) 6.15 (s, 2 H) 7.12 (d, J=9.35 Hz, 1 H) 7.66 (dd, J=8.72, 1.39 Hz, 1 H) 7.93-8.01 (m, 2 H) 8.04 (d, J=8.84 Hz, 1 H) 8.10 (s, 1 H) 8.17 (s, 1 H) 8.26 (s, 1 H) 11.18 (s, 1 H). MS:m/z 414.2 (M+H)+. MP 250.2-251.6° C.

Provenance & Evidence