Reaction SMILES: [N:1]1([C:5]2[C:10]3=[C:11]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=4)[N:12]=[C:13]([CH3:14])[N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1.Br[C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][N:23]=1.C(=O)([O-])[O-].[K+].[K+]>[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+].CCCCCCC>[N:1]1([C:5]2[C:10]3=[C:11]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[C:19]=4[C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][N:23]=4)[N:12]=[C:13]([CH3:14])[N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: FC(F)(F)c1ccc(Br)nc1
Reactant: Cc1nc(-c2cnn(C)c2)c2c(N3CCC3)ncnn12
Agent: Cl[Pd+]
Agent: C=C[CH2-]
Agent: O=C([O-])[O-]
Solvent: CCCCCCC
Product: Cc1nc(-c2cnn(C)c2-c2ccc(C(F)(F)F)cn2)c2c(N3CCC3)ncnn12
Temperature: 102 °C
Reaction time: 1 h

Procedure:
4-(Azetidin-1-yl)-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine (10.0 g, 37.1 mmol), 2-bromo-5-(trifluoromethyl)pyridine (16.8 g, 74.3 mmol) and ground potassium carbonate (15.4 g, 111 mmol) were combined in a reaction flask, purged with nitrogen, and treated with degassed 1,4-dioxane (600 mL). To this mixture was added allylpalladium(II) chloride dimer (693 mg, 1.86 mmol), and the system was again purged with nitrogen. The reaction was heated to 102° C. for 36 hours, then cooled and concentrated in vacuo. The residue was partitioned between ethyl acetate (400 mL) and aqueous hydrochloric acid solution (1 N, 200 mL). The aqueous phase was neutralized with solid sodium bicarbonate and extracted with ethyl acetate (4×50 mL). The combined organic layers were washed with 1 N aqueous citric acid, then with saturated aqueous sodium bicarbonate solution. After treatment with Darco® activated carbon, the organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in a minimal amount of dichloromethane and concentrated under reduced pressure until it became a thick oil. Diethyl ether (100 mL) was added, and upon stirring of the mixture, a solid began to precipitate; stirring was continued for 1 hour at room temperature, and then the white solid was collected by filtration and washed with diethyl ether. Additional product in the mother liquor was isolated by concentrating the filtrate in vacuo and chromatographing the residue on an alumina column (Eluant: 70% ethyl acetate in heptane). The product from the column was recrystallized from warm 20% ethyl acetate in heptane to yield additional product as a white solid. Combined yield: 5.3 g, 12.8 mmol, 35%. This material was combined with the product of a similar reaction (total 15.5 g, 37.4 mmol), and further purified as follows. The material was dissolved in a mixture of ethyl acetate (100 mL) and 2-methyltetrahydrofuran (150 mL) at room temperature. SiliaBond® thiol (SiliCycle, 1.35 mmol/g, 15 g) was added, and the mixture was stirred for 20 hours, then filtered through Celite. The filtrate was treated with Darco® activated carbon (500 mg) and stirred for 15 minutes before being filtered and concentrated under reduced pressure. The resulting oil was azeotroped with a 1:1 mixture of heptane and ethyl acetate to provide an off-white solid, which was mixed with heptane (100 mL) and stirred at room temperature for 6 hours. Filtration provided the product as a white solid. Purification yield: 14.4 g, 34.7 mmol, 93%. LCMS m/z 415.0 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.17-2.26 (m, 2H), 2.70 (s, 3H), 3.3-3.8 (v br m, 2H), 3.8-4.3 (v br m, 2H), 4.18 (s, 3H), 7.63-7.66 (m, 1H), 7.66 (s, 1H), 7.79-7.83 (m, 2H), 8.95-8.96 (m, 1H).