Trimethylacetamide → HCID 178432101, compound

Participants

Reaction Steps

To a solution of trimethylacetamide (10 mg, 0.1 mmol) in DMF (0.5 mL) was added sodium hydride (60%, 5.2 mg, 0.13 mmol). After stirring for 5 minutes, 4-chlorophenylisothiocyanate (17 mg, 0.1 mmol) was added. The reaction mixture was stirred at 60° C. for one hour before being cooled down to room temperature. To this reaction mixture was then added 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]-oct-3-yl}-1H-benzimidazole (35 mg, 0.08 mmol), EDCI (19 mg, 0.1 mmol) and a catalytic amount of DMAP. After stirring at ambient temperature overnight, the reaction was quenched with water and extracted with dichloromethane (4×10 mL). The organic phase was washed with brine and dried over sodium sulfate. The solvent was removed and the residue was purified by flash chromatography on silical gel, eluting with a gradient of 0-15% methanol in ethyl acetate to afford N-[(1E)-[(4-chlorophenyl)amino](4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl) methylidene]-2,2-dimethylpropanamide as amorphous solid (20 mg, 38%). 1H NMR (400 MHz, DMSO-d6) δ 8.9 (s, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.39-7.33 (m, 6H), 7.22-7.19 (m, 1H), 7.13-7.05 (m, 3H), 6.61 (d, J=8.6 Hz, 2H), 4.51-4.47 (m, 1H), 3.80-3.40 (m, 2H), 3.26-3.13 (m, 4H), 2.46 (s, 3H), 2.37-2.30 (m, 2H), 2.14 (br, 2H), 1.85-1.71 (m, 10H), 1.56 (d, J=7.4 Hz, 2H), 0.88 (s, 9H). HRMS m/z (M+H)+ calcd: 665.3735, obsd: 665.3741.

Provenance & Evidence