反应详情

温度

70 °C

To a 3-neck 1 liter round bottom flask fitted with a mechanical stirrer, thermocouple, nitrogen inlet and a condenser is sequentially charged: 14.5 g of (R)-3-chloro-a-ethyl-2-thiopheneethanamine (Compound III), 10.9 grams of 4-chloro-3-nitropyridin-2(1H)-one (Compound II), 35 grams of 2-propanol (IPA) and 25 mL of N,N-diisopropylethylamine (DIPEA). The mixture is stirred at 70° C.±2+ C. for 7 hours before the reaction is allowed to cool overnight to room temperature (22° C.±3° C.). The mixture is concentrated to 41 4 g. of a syrup which is subsequently dissolved in 425 ml of ethyl acetate. This solution is washed with 125 mL of water, 2×50 mL of 5N ammonium chloride solution and 2×50 mL of saturated sodium chloride solution before drying over sodium sulfate: The solution is filtered, concentrated, and the resulting solid collected by filtration to give Compound IV, m.p. 150-152° C. Mass Spec. (EI), m/z 328 (6%), 1H NMR (500 Mhz, DMSO) δ0.91 (3H, t); 1.8-1.6 (2H, m); 3.1 (1H, m); 3.95 (1H, m); 5.9 (1H, d); 7.0 (1H, d); 7.3 (1H, dd); 7.5 (1H, d); 8.8 (1H, d); 11.1 (1H).

1. customTo a 3-neck 1 liter round bottom flask fitted with a mechanical stirrer
2. additionthermocouple, nitrogen inlet and a condenser is sequentially charged
3. temperatureto cool overnight to room temperature (22° C.±3° C.)
4. concentrationThe mixture is concentrated to 41 4 g
5. dissolutionof a syrup which is subsequently dissolved in 425 ml of ethyl acetate
6. washThis solution is washed with 125 mL of water, 2×50 mL of 5N ammonium chloride solution and 2×50 mL of saturated sodium chloride solution
7. dry with materialbefore drying over sodium sulfate
8. filtrationThe solution is filtered
9. concentrationconcentrated
10. filtrationthe resulting solid collected by filtration