S-Methyl isothiourea sulfate

Methylene bis(guanidinomethane), CH2(-CHa.NH.C( NH).NH2)2 mw 158.21, N 53.16% hygr crysts, mp 135° sol in ale 8t w. Prepd by creating methylene bis(aminomethane) with s-methyl isothiourea sulfate. More recently isolated as the dipicrote salt by heating a mixt of cyanamide, methylene bis(aminomethane), and methylene bis (aminomethane p-toluene-sulfcnate), then treating with PA for the dipicrate mw 616.42, N 27.27%, OB —77.9%, mp 242°. Their expl props were not investigated... 

Methyl ami noguanidine, (CH3)NH-NH C(NHa) NH or (CHj)HN-N C(NHa )a, was prepd as the sulfate by heating on a water bath coned solns of methylhydrazine and S-methyl-isothiourea sulfate. It was patented in Germany... 

Szab6, C., Southan, G. J., and Thiemermann, C. (1994e). Beneficial effects and improved survival in rodent models of septic shock with S-methyl-isothiourea sulfate, a novel, potent and selective inhibitor of inducible nitric oxide synthase. Proc. Natl. Acad. Sci. U.S.A. 91, 12472-12476. 

The process starts from a Knovengol condensation of ethyl isobutyryl acetate with 4-fluorobenzaldehyde. The reaction of S -methyl isothiourea sulfate with a,P-unsaturated ketone followed by oxidation with DDQ gives 2-(methylthio)pyrimidine. This intermediate was further oxidized by w-CPBA to yield 2-(methylsulfonyl)pyrimidine. Aromatic substitution with methyl amine and sulfonylation afford methanesulfonamide derivative. The required alcohol can be synthesized by DIBAL reduction of the corresponding ester as... 

The alkyl esters of N-benzimidazol-2-yl-carbamic acid (22) can be prepared by the methylation of thiourea with dimethyl sulfate and the subsequent N-acylation in alkaline medium of the S-methyl-isothiourea formed (23) with the alkyl ester of chloroformic acid. Finally, N,N -bis(alkoxycarbonyl)-S-methylthiourea (24), obtained as an intermediate product is condensed with o-phenylene diamine in glacial acetic acid. 

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