1,4-Diazabicyclo(2.2.2)octane--trimethylalumane (1/2) → 2-N-Methyl-2-N-phenyl-6-{5-[(4-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}piperidin-1-yl)carbonyl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamine

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Bis(trimethylaluminum)-1,4-diazabicyclo[2.2.2]octane adduct (225 mg, 0.88 mmol) was added to 4-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}piperidine hydrochloride (Intermediate 267, 219 mg, 0.88 mmol) in dry THF (6 mL) in a sealed tube at room temperature. The reaction mixture was stirred at 40 C for 2 h. Ethyl 3-{4-amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazole-5-carboxylate (prepared in an analogous manner to Example 73, 200 mg, 0.58 mmol) was added at 40 C. The reaction was heated at 80 C for 2 h before being concentrated under vacuum. The residue was taken up in DMSO (6 mL) and the inorganic residue was filtered off. The filtrate was purified by preparative HPLC, Method C, to provide two batches of the title compound (batch 1: 33 mg, 11%). Some impure product was recovered from the preparative HPLC purification, this material was concentrated, diluted with water (50 mL), acidified with a 1N aq. solution of HCl (to pH 4) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (50 mL) and dried over magnesium sulfate. This crude material was then purified by preparative HPLC, Method C, to provide the title compound (Batch 2: 83 mg, 28%).

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