Triethylamine → ethyl 1'-{(R)-3-(4-benzyloxy-3,5-dimethyl-phenyl)-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 400 mg (0.70 mmol) (R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1g), 250 mg (0.78 mmol) TBTU and 0.12 mL (3.73 mmol) triethylamine in 20 mL THF were stirred for 1 h at RT. Then 0.4 mL (2.87 mmol) triethylamine and 270 mg (0.86 mmol) ethyl[1,4′]bipiperidinyl-4-carboxylate (used as the bis-hydrochloride salt) were added. The reaction mixture was stirred for 24 h at RT, diluted with EtOAc, washed with saturated NaHCO3 solution and the organic phase was dried on Na2SO4. After the elimination of the desiccant and solvent the residue was purified by chromatography (Alox activity stage II-III, gradient DCM/EtOH 40:1 to DCM/EtOH 30:1).

Provenance & Evidence