反应详情

A mixture of crude N-{2-[(2-guanidinothiazol-4-yl)methylthio]ethyl}ethanediimidamide trihydrochloride (5.65 g, 13.7 mmoles) [prepared in Step A], 50 ml of CH2Cl2 and 5.7 ml of triethylamine was treated with N,N'-thiobisphthalimide (DMF solvate) (5.44 g; 13.7 mmoles) and stirred for one hour to give a thick suspension. The mixture was treated with 40 ml of 2N NaOH and the solvents were decanted from the gum-like material which had separated. The gum was washed with 40 ml of 2N NaOH, water, and then dissolved in methanol and concentrated to give 3.0 g of crude product. The product was purified by flash chromatography on 90 g of silica gel (230-400 mesh) using ethyl acetate-methanol (97:3) as the eluent to give 2.44 g (54%) of the title compound. Treatment of the product in 35 ml of acetone with one equivalent of cyclohexylsulfamic acid gave the salt which was then recrystallized from 95% aqueous ethanol to give the title compound as its cyclohexylsulfamate salt, mp. 171°-173.5° C.

1. customto give a thick suspension
2. customthe solvents were decanted from the gum-like material which
3. customhad separated
4. washThe gum was washed with 40 ml of 2N NaOH, water
5. dissolutiondissolved in methanol
6. concentrationconcentrated
7. customto give 3.0 g of crude product
8. customThe product was purified by flash chromatography on 90 g of silica gel (230-400 mesh)