反应详情

To a 50 ml round-bottomed flask equipped with condenser and N2 inlet were added 2.4 g (7.53 mmol) of 4-(4-(2-chloroethyl)phenyl)-2-aminothiazole hydrobromide, 1.65 g (7.53 mmol) of N-(3-benzisothiazolyl) piperazine (prepared according to the method of U.S. Pat. No. 4,411,901), 1.3 ml (7.53 mmol) of diisopropylethylamine, 1.6 g (15.1 mmol) of sodium carbonate, 2 mg of sodium iodide, and 25 ml of methylisobutylketone. The reaction was heated at reflux for 5 days, cooled, evaporated, and taken up in ethyl acetate/water. The ethyl acetate layer was separated, washed with water and brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using ethyl acetate as eluent to give a solid. The solid was taken up in hot ethyl acetate, precipitated by addition of hydrochloride gas, the precipitate filtered, washed with ether, and dried to give a beige solid, 1.536 g (38%), m.p. >300° C. (dec.). NMR (DMSO-d6): 3.2-3.8 (m, 10H), 4.1 (m, 2H), 7.25 (s, 1H), 7.4-8.2 (m, 8H), 11.5 (bs, 2H).

1. customTo a 50 ml round-bottomed flask equipped with condenser and N2 inlet
2. customprepared
3. temperatureThe reaction was heated
4. temperatureat reflux for 5 days
5. temperaturecooled
6. customevaporated
7. customThe ethyl acetate layer was separated
8. washwashed with water and brine
9. dry with materialdried over sodium sulfate
10. customevaporated
11. customThe residue was chromatographed on silica gel
12. customto give a solid
13. customprecipitated by addition of hydrochloride gas
14. filtrationthe precipitate filtered
15. washwashed with ether
16. customdried
17. customto give a beige solid, 1.536 g (38%), m.p. >300° C. (dec.)