Hexachloroethane → 3,5-Dimethyl-4-[8-(2,3,4-trifluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

To a solution of 8-(2,3,4-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (prepared in analogy to example 66a-c) (300 mg, 1.14 mmol) and hexachloroethane (296 mg, 1.25 mmol) in dry THF (8 mL) was added triethylamine (287 mg, 396 μL, 2.84 mmol) under an argon atmosphere followed by trimethylphosphine (1 M in THF, 1.25 mL, 1.25 mmol). The reaction mixture was stirred at room temperature for 45 minutes, then (3R,5S)-tert-butyl 3,5-dimethyl-4-oxopiperidine-1-carboxylate (315 mg, 1.25 mmol) added and the mixture heated to 150° C. in the microwave for 3 hours. A solution of decaborane (139 mg, 148 μL, 1.14 mmol) in MeOH (3 mL) was added to the reaction mixture and stirred at 50° C. for 2 hours. Further decaborane (139 mg, 148 μl, 1.14 mmol) in MeOH (3 mL) was added and stirred at 50° C. for another 2 hours. The reaction mixture was poured in water and extracted with dichloromethane. The organic layers were combined, dried over Na2SO4 and evaporated. The residue was purified by flash-chromatography over 70 g SiO2-flash pack using gradient 0-100% EtOAc in heptane over 35 minutes to give the title compound as off-white foam (208 mg, 39%) as a mixture of cis- and trans-isomers. MS ISP (m/e): 476.2/420.2/376.3 (13/40/62) [(M+H)+/(M−tBu)+/(M−Boc)+].

Provenance & Evidence