反应详情

温度

110 °C

As shown in step 17-v of Scheme 17, to Compound 2058 (293 mg, 0.85 mmol), 2,3-dimethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (269 mg, 1.01 mmol), Na2CO3 (179 mg, 1.69 mmol), and Pd(PPh3)4 (98 mg, 0.085 mmol) was added DMF (10 mL), followed by the addition of water (2 mL). The reaction vessel was evacuated, placed under an atmosphere of nitrogen, then warmed to 110° C. (sand bath). After 16 hours the reaction mixture was partitioned between EtOAc and water (100 mL each). The organics were washed with water (70 mL), brine (70 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was dissolved/suspended in EtOAc (7 mL) and heated with swirling in a water bath at 50° C. for 40 minutes. The resulting mixture was treated with hexanes (5 mL) and swirled an additional 5 minutes at 50° C. After cooling to 23° C., the resulting solid was collected by filtration and washed with 1:1 (EtOAc:hexanes, 5 mL) to give 2-(5,6-dimethoxypyridin-3-yl)-7-methoxy-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (Compound 256) as a mixture of enantiomers: ESMS (M+H) 450.44; 1H NMR (CDCl3, 300 MHz) δ 8.57 (d, J=3 Hz, 1H), 8.35 (s, 1H), 8.27 (s, 2H), 7.99 (d, J=3 Hz, 1H), 7.93 (s, 1H), 6.40 (s, 1H), 5.22 (q, J=9 Hz, 2H), 3.96 (s, 3H), 3.93 (s, 3H), 3.13 (s, 3H).

1. customThe reaction vessel was evacuated
2. customAfter 16 hours the reaction mixture was partitioned between EtOAc and water (100 mL each)
3. washThe organics were washed with water (70 mL), brine (70 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. temperatureheated
8. additionThe resulting mixture was treated with hexanes (5 mL)
9. waitswirled an additional 5 minutes at 50° C
10. temperatureAfter cooling to 23° C.
11. filtrationthe resulting solid was collected by filtration
12. washwashed with 1:1 (EtOAc:hexanes, 5 mL)