反应详情

Guanidine nitrate (244 g.) was slurried in dimethylformamide (500 ml., dried over molecular sieve) and sodium hydride paste (58 g. of a 63% w/w dispersion in oil) was added over 30 minutes with external cooling in an acetone/solid CO2 bath to maintain the internal temperature at 25°-30°. The mixture was stirred for 30 minutes at 25° then cooled to 20°. 5-Chloro-3-chloromethyl-1,2,4-thiadiazole (84.5 g.) was added at 20°-25° over 20 minutes with external cooling at 5°-10°. The mixture was stirred for 20 minutes at 25° then poured into water (5000 ml.) and extracted with ethyl acetate (2×5000 ml.). The combined upper layers were extracted with 2 N HCl (2×500 ml.) and the combined acid extracts were basified with 2 N NaOH. The product was filtered off, washed with water, sucked dry and then dried over P2O5 at 1 m.m. to give 3-chloromethyl-5-guanidino-1,2,4-thiadiazole.

1. additionof a 63% w/w dispersion in oil) was added over 30 minutes
2. temperaturewith external cooling in an acetone/solid CO2 bath
3. temperatureto maintain the internal temperature at 25°-30°
4. temperaturethen cooled to 20°
5. temperaturewith external cooling at 5°-10°
6. stirringThe mixture was stirred for 20 minutes at 25°
7. extractionextracted with ethyl acetate (2×5000 ml.)
8. extractionThe combined upper layers were extracted with 2 N HCl (2×500 ml.)
9. filtrationThe product was filtered off
10. washwashed with water
11. customsucked dry
12. dry with materialdried over P2O5 at 1 m