Triethylamine → Diethylether hexane

Methanesulfonyl chloride (0.01 mL, 0.136 mmol, 1.2 equiv.) was added dropwise via a syringe to a stirred, −30° C. solution of 1-[6-(2-hydroxy-ethyl)-naphthalen-2-yl]-1H-pyridin-2-one (Example 80A, 30 mg, 0.113 mmol) and Et3N (0.024 mL, 0.17 mmol, 1.5 equiv.). After two hours stirring at room temperature, 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 and the residue was crystallized from Et2O/hexane (20 mg, 52% yield). This mesylate (20 mg, 0.058 mmol), (2R)-2-methylpyrrolidine (14.9 mg, 0.058 mmol, 3.0 equiv.), and cesium carbonate (19 mg, 0.058 mmol) in anhydrous acetonitrile (3.5 mL) were stirred in a sealed tube at 60° 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 HCl gas was bubbled in to precipitate the hydrochloride salt of the title compound. 1H NMR (CD3OD, 300 MHz) δ 8.08–7.96 (m, 2H), 7.93 (s, 2H), 7.76–7.66 (m, 2H), 7.60–7.51 (m, 2H), 6.70 (d, J=9 Hz, 1H), 6.56 (dt, J=1, 6 Hz, 1H), 3.83–3.68 (m, 2H), 3.64–3.49 (m, 1H), 3.43–3.18 (m, 4H), 2.43–2.30 (m, 1H), 2.22–2.02 (m, 2H), 1.84–1.69 (m, 1H), 1.49 (d, J=6 Hz, 3H). MS (DCI-NH3) [M+H]+ at 333.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. customThe residue was partitioned between EtOAc and saturated aqueous Na2CO3
3. extractionThe organic extract
4. dry with materialwas dried (MgSO4)
5. filtrationfiltered
6. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-f308d08c1d2c4b6890eb7f09f0b254a0

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153889B2