3,4-Dimethoxy-1,2,5-thiadiazole 1-oxide → HCID 86742185, compound

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Reaction Steps

A solution of 2-[2-(2,2,2-trifluoroethyl)guanidino]-4-[(2-aminoethyl)thiomethyl]thiazole (European Patent Publication No. 30092, Example 2; 2.1 g.) in methanol (20 ml.) was added dropwise to a stirred solution of 3,4-dimethoxy-1,2,5-thiadiazole 1-oxide (UK Patent Application No. 2067987, Example 4; 1.1 g.) in methanol (50 ml.) at 5°. The solution was stirred for 1.5 hours at 5°-10°. The intermediate 3-methoxy-4-[2-(2-[2,2,2-trifluoroethyl]-guanidino)thiazol-4-ylmethylthio]ethylamino-1,2,5-thiadiazole 1-oxide was not isolated, but anhydrous ammonia in methanol (6M, 20 ml.) was added. The solution was stirred for 17 hours at 25° and the solvent was evaporated. The residue was purified by chromatography on silica gel using dichloromethane/methanol 9:1 v/v as eluant. The purified product was obtained as an oil which was dissolved in acetone and the solution was treated with an excess of maleic acid in acetone. The salt which precipitated was recrystallized from ethyl acetate/ethanol to give 3-amino-4-[2-(2-[2,2,2-trifluoroethyl]guanidino)thiazol-4-ylmethylthio]ethylamino-1,2,5-thiadiazole 1-oxide maleate (2.0 g.), m.p. 113° (decomp.) having the following n.m.r. spectrum in d6 dimethylsulphoxide: 2.8 (t, 2H); 3.55 (t, 2H); 3.7 (s, 2H); 4.15 (q, 2H); 6.2 (s, 2H); 6.8 (s, 1H).

Provenance & Evidence