Triethylamine → 3-[1,4']Bipiperidinyl-1'-ylmethyl-2-phenyl-quinoline-4-carboxylic Acid ((S)-1-cyclohexyl-ethyl)-amide Dihydrochloride

Participants

Reaction Conditions

Reaction Steps

4.0 g (8.0 mmol) of crude 3-[1,4′]bipiperidinyl-1′-ylmethyl-2-phenyl-quinoline-4-carboxylic acid dihydrochloride (compound of Description 2) were dissolved in 300 ml of a 1:1 mixture of CH2Cl2/CH3CN; 3.4 ml (24.6 mmol) of triethylamine (TEA) and 4.0 g (10.7 mmol) of O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HBTU) were added and the reaction mixture was cooled at 0° C. 1.22 ml (8.2 mmol) of (S) 1-cyclohexylethylamine, dissolved in 10 ml of dry CH2Cl2, were added dropwise and the reaction mixture was stirred at room temperature for 24 h. Additional 2.0 g (5.3 mmol) of HBTU and 2.0 ml (13.4 mmol) of (S)-1-cyclohexyl-ethylamine were added and the reaction mixture was heated to 40° C. for 8 h. The solvent was evaporated in vacuo to dryness and the residue was taken up with EtOAc and washed with H2O, 1 N NaOH and brine, dried over Na2SO4 and evaporated to dryness to yield a crude material which was purified by flash column cromatography on 230-400 mesh silica gel, utilising a mixture of EtOAc/MeOH 95:5 containing 0.5% NH4OH (28%). The residue was dissolved in acetone and acidified with HCl/Et2O; the precipitate so formed was recovered by suction filtration to yield 3.2 g of title compound as a pale yellow solid.

Provenance & Evidence