Triethylamine → cis-N-(3-{4-[4-(Octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-3-oxo-propyl)-methanesulfonamide

Participants

Reaction Steps

To a solution of cis-(octahydro-quinolin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)-methanone (CC-033) (0.065 g, 0.20 mmol) in acetonitrile (1 mL) was added triethylamine (0.59 mmol), HATU (0.22 mmol) and N-t-butyloxycarbonyl β-alanine (0.22 mmol). The reaction mixture was stirred for 4 hours, and then the solvent was removed by evaporation. The residue was dissolved in TFA (2 mL) and DCM (2 mL) and the reaction mixture stirred for 2 hours. The solvent was evaporated and the residue purified by flash chromatography on an SCX-2 cartridge, eluting with acetonitrile and then 2 M ammonia in methanol. The fractions containing 3-amino-1-{4-[4-(octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-propan-1-one were concentrated under vacuum to a colourless oil (0.089 g). The oil was dissolved in DCM (1 mL) and triethylamine (0.33 mmol) and methanesulphonyl chloride (0.22 mmol) were added. The mixture was stirred for 18 hours and then diluted with water and DCM. The organic solution was separated, dried and the solvent evaporated. The residue was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid). The fractions containing the desired product were concentrated under vacuum to give the title compound as a colourless oil (0.047 g). LCMS mk 482.09 [M+H]+ RT=9.52 min (Analytical Method 2).

Provenance & Evidence