Cn1nccc1CCOc1ccc(C2CCNCC2)cc1.FC(F)(F)c1nnc2ccc(Br)cn12>CC(C)(C)[O-].Cc1ccc(C)cc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>Cn1nccc1CCOc1ccc(C2CCN(c3ccc4nnc(C(F)(F)F)n4c3)CC2)cc1
6-bromo-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (65 mg, 0.24 mmol), 4-(4-(2-(1-methyl-1H-pyrazol-5-yl)ethoxy)phenyl)piperidine (112 mg, 0.24 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (11.41 mg, 0.02 mmol) and Sodium tert-butoxide (0.060 mL, 0.49 mmol) were suspended in xylenes (5 mL), then de-gassed and purged with nitrogen. Bis(dibenzylideneacetone)palladium (7.02 mg, 0.01 mmol) was added, and the mixture was sealed into a microwave tube. The reaction was heated to 110 °C for 30 minutes in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (25 mL), and washed with water (25 mL). The aqueous layer was extraced with further EtOAc (25 mL). The combined organic layers were purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-(4-(4-(2-(1-methyl-1H-pyrazol-5-yl)ethoxy)phenyl)piperidin-1-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (22.00 mg, 19.14 %) as a colourless gum.
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