Diisopropylethylamine → {3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-[4-(trifluoromethyl)phenyl]piperidin-1-yl}(morpholin-4-yl)methanone

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Reaction Steps

Under argon, a solution of 11.9 g (30.7 mmol) of carboxylic acid from Example 4A in 150 ml of DMF was admixed at RT with 19.2 g (36.8 mmol) of PYBOP and 10.7 ml (61.4 mmol) of N,N′-diisopropylethylamine. Subsequently, the mixture was stirred at RT for 30 min and then the solution was added dropwise within 1.5 h to a suspension of 24.5 g (92.1 mmol) of hydroxyguanidine hemisulphate hemihydrate, 16.1 ml (92.1 mmol) of N,N′-diisopropylethylamine and 4 Å molecular sieve. The reaction mixture was stirred at RT for 1 h and then filtered through a frit. The residue was washed with 200 ml of DMF and then the combined organic phases were stirred at 130° C. (preheated oil bath) for 1.5 h. Subsequently, the solvent was removed under reduced pressure and the residue was admixed with 300 ml of diethyl ether and 300 ml of 1 N aqueous sodium hydroxide solution, and stirred vigorously for 24 h. The solid formed was filtered off, washed with water and diethyl ether and then dried under high vacuum. Yield: 8.80 g (66% of theory)

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