Triethylamine → Ethyl 1'-{(r)-3-(4-methyl-2-oxo-2,3-dihydro-benzoxazol-6-yl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1,4'-bipiperidinyl-4-carboxylate

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Reaction Steps

A solution of 300 mg (0.59 mmol) (R)-1-carboxy-2-(4-methyl-2-oxo-2,3-dihydrobenz-oxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5,-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate, 210 mg (0.65 mmol) TBTU and 100 μL (0.72 mmol) triethylamine in 20 mL THF was stirred for 1 h at RT. Then 220 mg (0.70 mmol) ethyl [1,4′]bipiperidinyl-4-carboxylate (used as the bis-hydrochloride salt) and 400 μL (2.87 mmol) triethylamine were added. The reaction mixture was stirred for 24 h at RT. The mixture was diluted with EtOAc, the organic phase was washed with saturated NaHCO3 solution and dried on Na2SO4. After the desiccant and solvent had been eliminated the residue was purified by chromatography (Alox, activity grade II-III, gradient DCM/EtOH 20:1 to DCM/EtOH 10:1). The fractions containing the product were combined, evaporated down i. vac., the residue was triturated with diethyl ether, suction filtered and dried.

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