反应详情

温度

110 °C

A mixture of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 0.20 g, 0.56 mmol), 5-bromo-2-ethylpyrimidine (0.13 g, 0.68 mmol), Binap-rac (0.035 g, 0.056 mmol), Pd(OAc)2 (0.013 g, 0.056 mmol), and Cs2CO3 (0.92 g, 2.8 mmol) were combined in degassed toluene (6 mL) and stirred in a sealed tube at 110° C. overnight. The solution was cooled, quenched with water, extracted with EtOAc, dried over MgSO4, and concentrated. Flash chromatography (2% MeOH in EtOAc) of the crude material, followed by trituration of the crude product with 9:1 hexanes:DCM gave a white solid that was filtered and dried. The material was characterized as (S)-1-(1-(2-ethylpyrimidin-5-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.010 g, 0.023 mmol, 4% yield). 1H NMR (400 MHz, CDCl3) δ 1.20 (t, 3H), 1.61-1.92 (m, 5H), 2.47 (q, 2H), 2.60-2.70 (m, 1H), 2.90-3.03 (m, 2H), 3.03 (s, 3H), 3.30-3.47 (m, 2H), 4.10-4.17 (m, 1H), 4.25-4.38 (m, 1H), 4.83-4.92 (m, 2H), 5.10 (s, 1H), 6.80 (t, 1H), 7.55 (d, 1H), 7.60 (d, 1H), 7.70 (s, 2H). Optical purity was not determined.

1. temperatureThe solution was cooled
2. customquenched with water
3. extractionextracted with EtOAc
4. dry with materialdried over MgSO4
5. concentrationconcentrated
6. customDCM gave a white solid
7. filtrationthat was filtered
8. customdried