反应详情

To a stirred solution of N-[5-(7-tert-Butyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-2-(4-fluoro-phenyl)-acetamide (Example 546, 115 mg, 0.27 mmol) in anhydrous THF (4.5 mL), was added NaH (60% in paraffin oil, 10.7 mg, 0.27 mmol) at 0° C. under nitrogen and the resulting mixture stirred for 10 min. MeI (0.017 mL, 0.27 mmol) was then added and the reaction mixture was stirred at room temperature for 1 hour. Aqueous saturated ammonium chloride (5 mL) was added and the mixture extracted with ethyl acetate (2×10 mL). The organic phase was washed with water (10 mL), brine (10 mL), dried over sodium sulphate and evaporated to dryness in vacuo. The crude material was purified via preparative TLC (eluting with 5% methanol in DCM) to afford the title compound as off white solid in 46% yield, 55 mg. 1H NMR (400 MHz, DMSO-D6) δ: 1.79 (s, 9H), 3.28 (s, 3H), 3.58 (br, 2H), 7.08-7.20 (m, 4H), 8.20 (s, 1H), 8.32 (s, 1H), 8.83 (s, 1H), 8.97 (br, 1H), 9.01 (s, 1H), 9.50 (s, 1H); LCMS (system 10): Rt=3.08 min; m/z 446 [M+H]+.

1. stirringthe reaction mixture was stirred at room temperature for 1 hour
2. extractionthe mixture extracted with ethyl acetate (2×10 mL)
3. washThe organic phase was washed with water (10 mL), brine (10 mL)
4. dry with materialdried over sodium sulphate
5. customevaporated to dryness in vacuo
6. customThe crude material was purified via preparative TLC (eluting with 5% methanol in DCM)