Triethylamine → HCID 57419171, compound

Participants

Reaction Conditions

Reaction Steps

Methanesulfonyl chloride (0.03 mL, 0.301 mmol, 1.2 equiv.) was added dropwise via a syringe to a stirred, 0° C. solution of 1-[6-(2-hydroxy-ethyl)-naphthalen-2-yl]-4-methyl-1H-pyridin-2-one (Example 82A, 70 mg, 0.251 mmol) in anhydrous THF (10 mL) under a dry nitrogen atmosphere. Triethylamine (1.0 mL, 7.175 mmol, 28.6 equiv.) was then added. After two hours of stirring at 0° C., the reaction mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc and saturated aqueous Na2CO3. The organic extract was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. This crude mesylate (˜89 mg, 0.249 mmol), (2R)-2-methylpyrrolidine (64 mg, 0.747 mmol, 3.0 equiv.), and cesium carbonate (81 mg, 0.249 mmol) in anhydrous acetonitrile (5 mL) were stirred in a sealed tube at 50° C. for 18 hours. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous Na2CO3. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (97:3:trace dichloromethane/methanol/NH4OH). Fractions containing product were combined and concentrated under reduced pressure to provide the free base. This free base was dissolved in Et2O and the solution was treated with HCl-dioxane to precipitate the hydrochloride salt of the title compound (15 mg, 16% yield). 1H NMR (CD3OD, 300 MHz) δ 8.00 (d, J=9 Hz, 1H), 7.98 (d, J=9 Hz, 1H), 7.93-7.89 (m, 2H), 7.62 (d, J=7 Hz, 1H), 7.56 (dd, J=2, 9 Hz, 1H), 7.51 (dd, J=2, 9 Hz, 1H), 6.52 (br s, 1H), 6.45 (dd, J=2, 7 Hz, 1H), 3.83-3.68 (m, 2H), 3.61-3.49 (m, 1H), 3.43-3.17 (m, 4H), 2.43-2.30 (m, 1H), 2.33 (s, 3H), 2.24-1.99 (m, 2H), 1.83-1.69 (m, 1H), 1.49 (d, J=6 Hz, 3H). MS (DCl-NH3) [M+H]+ at 347.

Provenance & Evidence