反应详情

To a solution of (S)-3,5-dichloro-1-(1-cyclopropyl-2-methoxyethyl)pyrazin-2(1H)-one (4.00 g, 15.2 mmol) from Part G and 6-methoxy-2,5-dimethylpyridin-3-amine (2.31 g, 15.2 mmol) from Part K in THF (76 mL) at 0° C. was added NaHMDS (31.9 mL, 31.9 mmol, 1 M in THF). The reaction mixture was stirred at room temperature for 1 h. The mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution. The aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (10% 40% ethyl acetate in hexanes) to afford (S)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(6-methoxy-2,5-dimethylpyridin-3-ylamino)pyrazin-2(1H)-one (4.94 g, 86% yield) as a light-brown amorphous solid. Recrystallization from hexanes/ethyl acetate (1:1, 10 mL) to afforded a light-brown crystalline solid: mp 99-100.5° C.; [α]25D −52.3 (c 0.636, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.88 (s, 1H), 6.90 (s, 1H), 4.19-4.14 (m, 1H), 3.92 (s, 3H), 3.74 (dd, JAB10.3, JAX=6.2 Hz, 1H), 3.67 (dd, JBA=10.3, JBX=3.5 Hz, 1H), 3.34 (s, 3H), 2.41 (s, 3H), 2.17 (s, 3H), 1.31-1.24 (m, 1H), 0.80-0.73 (m, 1H), 0.62-0.56 (m, 1H), 0.53-0.47 (m, 1H), 0.36-0.30 (m, 1H); HRMS (ESI) m/e 379.1537 [(M+H)+, calcd for C18H24N4O3Cl 379.1537].

1. customThe mixture was transferred to a separatory funnel
2. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
3. washThe combined organic layers were washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by column chromatography on silica gel (10% 40% ethyl acetate in hexanes)