反应详情

温度

120 °C

A mixture of 2-(2,4,6-trifluoro-phenyl)-malonic acid diethyl ester (200 g, 0.67 mol), pyrazine-2-carboxamidine hydrochloride (132 g, 0.828 mol) and potassium carbonate (114 g, 0.828 mol) in 2-methyoxyethyl ether (diglyme, 600 mL) is heated to 120° C. and stirred for 4 h, then heated to 140° C. and stirred for an additional 2 h. The mixture is cooled to room temperature (25–30° C.) and water (1200 mL) is added over about 15 min. Acetic acid (50 g) is added over 15 min. and 82 ml of concentrated HCl is added over 15 min and the mixture is stirred for about 15 min. at room temperature at a pH of about 2–3. The solid is filtered and washed with water (2×400 mL) and isopropyl alcohol (IPA) (400 mL) and dried at 60° C./10 mmHg for 24 h to give a white solid 69% yield with 95% HPLC purity. 1H NMR (DMSO-d6): d 12.45 (bs, 2H), 9.41(s,1H), 8.91(s,1H), 8.46(m, 1H), 7.23(m, 2H).

1. temperatureheated to 140° C.
2. stirringstirred for an additional 2 h
3. additionis added over about 15 min
4. stirringthe mixture is stirred for about 15 min. at room temperature at a pH of about 2–3
5. filtrationThe solid is filtered
6. washwashed with water (2×400 mL) and isopropyl alcohol (IPA) (400 mL)
7. customdried at 60° C./10 mmHg for 24 h