Reaction SMILES: Br[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH3:19])[N:11]2[C:16]=1[C:15]([NH:17][CH3:18])=[N:14][CH:13]=[N:12]2.[F:20][CH:21]([F:37])[C:22]1[CH:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl.[OH-].[Na+]>C(O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:20][CH:21]([F:37])[C:22]1[CH:27]=[CH:26][C:25]([C:2]2[N:6]([CH3:7])[N:5]=[CH:4][C:3]=2[C:8]2[N:9]=[C:10]([CH3:19])[N:11]3[C:16]=2[C:15]([NH:17][CH3:18])=[N:14][CH:13]=[N:12]3)=[CH:24][CH:23]=1
Reactant: CNc1ncnn2c(C)nc(-c3cnn(C)c3Br)c12
Reactant: CC1(C)OB(c2ccc(C(F)F)cc2)OC1(C)C
Agent: [Pd]
Agent: Cl
Agent: O=P([O-])([O-])[O-]
Solvent: CCO
Solvent: O
Product: CNc1ncnn2c(C)nc(-c3cnn(C)c3-c3ccc(C(F)F)cc3)c12
Temperature: 70 °C
Reaction time: 16 h

Procedure:
[5-(5-Bromo-1-methyl-1H-pyrazol-4-yl)-N,7-dimethylimidazo[5,1-f][1,2,4]triazin-4-amine (13.01 g, 40.38 mmol) and 2-[4-(difluoromethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (12.75 g, 50.18 mmol) were combined in ethanol (126 mL), and the resulting slurry was treated with a solution of potassium phosphate (98%, 11.04 g, 50.97 mmol) in water (42 mL) and warmed to 70° C. over 30 minutes while a vigorous nitrogen flow was applied through a bubbler. After addition of tetrakis(triphenyl phosphine) palladium(0) (481 mg, 0.416 mmol), the reaction mixture was heated at reflux for 4 hours, then cooled to room temperature and stirred for an additional 16 hours. The mixture was filtered through a plug of cotton, and the filtrate was concentrated in vacuo, then reconcentrated with 2-methyltetrahydrofuran (2×150 mL). The residue was reconstituted in 2-methyltetrahydrofuran (150 mL) and extracted with aqueous hydrochloric acid (1 M, 70 mL, stirred for 20 minutes). The aqueous layer (pH ˜2-3) was discarded. The organic layer was extracted twice with 1 M aqueous hydrochloric acid: first with 100 mL (stirring for 1 hour), then with 75 mL (stirring for 20 minutes). The 100 mL aqueous layer was back-extracted with 2-methyltetrahydrofuran (75 mL, stirred for 20 minutes) to remove a light yellow color; from this organic layer precipitated a solid, which was collected and rinsed with tert-butyl methyl ether to provide X-ray quality crystals. Single crystal X-ray analysis revealed this material to be the monohydrate of the hydrochloride salt of the product. The two hydrochloric acid layers were combined and treated with aqueous sodium hydroxide solution (5 M, 35.5 mL), which adjusted the pH to 6. The resulting mixture was extracted with 2-methyltetrahydrofuran (150 mL); the organic layer was passed through a plug of sodium sulfate (58 g) and concentrated in vacuo to a volume of roughly 150 mL. This yellow solution was treated with Darco® G-60 activated carbon (5.03 g), and spun on a rotary evaporator in a 50° C. water bath for 1.5 hours. The warm solution was filtered through a pad of Celite, and the filtrate was concentrated under reduced pressure. The resulting light yellow solid was treated with tert-butyl methyl ether (250 mL) and spun on a rotary evaporator in a 55° C. water bath for 1 hour. Roughly 100 mL of solvent was removed using the rotary evaporator, and the resulting mixture was cooled to room temperature with stirring over 1 hour. The slurry was then cooled in an ice bath and stirred for an additional 30 minutes. The solids were collected by filtration and rinsed with chilled tert-butyl methyl ether (cooled in ice—saturated aqueous sodium chloride solution bath; 50 mL) to provide the product as a powdery white solid. Yield: 11.27 g, 30.51 mmol, 76%. LCMS m/z 370.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.65 (br s, 3H), 2.98 (d, J=5.1 Hz, 3H), 3.94 (s, 3H), 5.48-5.55 (m, 1H), 6.65 (t, J=56.3 Hz, 1H), 7.52 (br AB quartet, JAB=8.4 Hz, ΔvAB=17.9 Hz, 4H), 7.73 (s, 1H), 7.90 (br s, 1H).