Trimethylsilylacetylene → HCID 9983820, compound

Participants

Reaction Steps

To a solution of 4-[4-benzo[1,3]dioxol-5-yl-5-(6-bromo-pyridin-2-yl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid benzyl ester (prepared in accordance with Scheme 1b with 6-bromo-piperidine-2-carbaldehyde as the starting material; 100 mg, 0.18 mmol) in DMF (1 mL) and triethylamine (2 mL) under nitrogen, was added PdCl2(PPh3)2 (2 mg, 0.005 mmol) and CuI (2 mg, 0.01 mmol), then followed with trimethylsilylacetylene (30 uL, 0.20 mmol). The mixture was stirred at room temperature for 4 hours until LC-MS showed complete coupling. Diethyl ether (30 mL) was added and the precipitate was filtered off. The clear solution was washed with saturated aqueous NH4Cl, then 0.5M EDTA solution, and water, and then dried (MgSO4). Concentration gave a yellow syrup that was dissolved in THF (20 mL). The solution was cooled to 0° C. and tetrabutylammonium fluoride (2 mL, 1 M in THF) was added. The mixture was stirred at room temperature for 30 minutes until LC-MS indicated complete removal of the silyl group. The reaction mixture was then concentrated in vacuum and passed through a short silica gel column with ethyl acetate/dichloromethane (1:1). The purified material was dissolved in ethanol (20 mL) and PtO2 (50 mg) was added. The mixture was stirred under hydrogen (1 atm) at room temperature for 3 days until LC-MS showed major conversion of the alkyne to the correponding alkane. The solids were filtered off and the filtrates were concentrated and purified on preparative HPLC to give the title compound (3 mg, 3%) as a TFA salt. MS (EPS+: 511.3 (MH+)). 1H NMR (400 MHz, MeOH-d4) δ 7.60 (t, 1H), 7.39-7.29 (m, 5H), 7.23 (d, 1H), 7.13 (d, 1H), 6.93 (dd, 1H), 6.91 (dd, 1H), 6.81 (d, 1H), 5.95 (s, 2H), 5.14 (s, 2H), 4.28 (d(br), 2H), 3.04 (m, 1H), 3.02 (br, 2H), 2.79 (q, 2H), 2.00 (d(br), 2H), 1.85 (ddd, 2H), 1.28 (t, 3H)

Provenance & Evidence