5-Methylisourea

Treatment of pyranone 15 with 2-methylisourea generates an imine which reacts inter-molecularly to provide the 1,5-diazocine system.38... 

Add 1.5 pi of the o-methylisourea hemisulfate solution to the peptide solution with mixing. 

The group of Lindau has demonstrated the effective O-alkylation of carboxylic acids using a polymer-supported O-methylisourea reagent [123], Under conventional conditions, complete esterifications were observed only after refluxing for several hours in tetrahydrofuran, and the acidic work-up required limited the scope of applicable substituents. In contrast, employing microwave heating led to complete esterifications within 15-20 min, with only 2 equivalents of the polymer-bound... 

The interaction (575) of O-methylisourea and N-methylglycine occurs normally at low temperatures to yield the expected creatine (XXXII) (21%). At 40—50° the production of 1-methyl-l-biguanide acetic acid (XXXIII) in low yield has been reported, but the mechanism of its formation ist not clear. 

A new variant of the Sn(ANRORC) substitutions was found in reactions of A-methylpyrimidinium salts with bifunctional nucleophiles, such as S-methylisourea, O-methylisourea, and cyanamide. 

When l-methyl-4-phenylpyrimidiniun iodide reacts with 5-methylisourea, it is converted in the corresponding 2-amino-4-phenylpyrimidine (yield 70%). A similar conversion has been reported for l-methyl-5-phenylpyrim-idinium iodide, 2-amino-5-phenylpyrimidine being obtained in 40% yield (Scheme III.47) (76RTC209). In both reactions, no detectable amounts of 2-methylthio-4-phenyl- or 2-methylthio-5-phenylpyrimidines are ob-... 

Methylisourea hydrochloride decomposes on heating with evolution of methyl chloride. The decomposition temperature depends on the rate of heating, but reproducible values are obtainable if the rate of heating is controlled. Samples of pure (98-99%) (Note 12) methylisourea hydrochloride, introduced... 

The purity of the crystallized product, determined volu-metrically by Volhard s method, exceeds 98%. In this procedure, 10 ml. of a 1% solution of methylisourea hydrochloride is acidified with a few drops of nitric acid and treated with 20 ml. of 0.1 N silver nitrate. After removal of the silver chloride by filtration, the excess of the silver nitrate is estimated with 0.1 TV thiocyanate solution, using ferric alum as indicator. Alternatively, 10-ml. portions of 0.1 N silver nitrate, acidified with nitric acid, may be titrated directly with the 1% methylisourea hydrochloride solution in the presence of tartrazine. 

Methylisourea hydrochloride may be safely stored over long periods if kept in small, well-stoppered, filled bottles, which are in turn placed in a desiccator. 

Methylisourea hydrochloride has been prepared by the action of hydrogen chloride on a suspension of silver cyanamide 2 or a solution of cyanamide3-4 in methanol,3 and by the action of dimethyl sulfate on urea at 112°.6 The free base is obtained by treating the salt with powdered potassium hydroxide in a water-ether mixture 3 or with sodium methoxide in methanol.0... 

To a flask containing 60 gm (1.0 mole) of urea is added 126 gm (1.0 mole) of methyl sulfate, and the stirred reaction mixture is warmed for 7 hr at 40°C. Stirring is continued until the reaction mixture is clear. The O-methylisourea is isolated as the picrate salt by adding 350-400 ml of 2 M lithium picrate in 300 ml of ethanol. The resulting mixture is boiled on the steam bath for 5 min. Most of the picrate dissolves but precipitates on slowly cooling to 0°C. The picrate is filtered, washed with ethanol, and air-dried to afford 182 gm (60%), m.p. 177°C. 

O-Methylisourea hydrogen sulphate (2-methylpseudourea sulphate) [29427-58-5] M 172.2, m 114-118 , 119 . Recrystd from MeOH-Et2O (327g of salt dissolved in IL of MeOH and 2.5L of Et20 is added) [Fearing and Fox JACS 16 4382 1954 ]. The picrate has m 192° [Odo et al. JOC 23 1319 1958]. iV-Methyl maleimide [930-88-1] M 111.1, m 94-96 . Crystd three times from ethyl ether. 

The synthesis of this ring system may be achieved by building the triazole onto a preformed pyrimidine ring. Cyclocondensation of ketoesters 330 with O-methylisourea (331) gave the pyrimidine 332, whose acylation gave the /V-acyl derivative 333, which can be cyclized with hydrazines to give 334 (89GEP3839711) (Scheme 64). 

Guanidination of all 10 t-amino groups with O-methylisourea causes loss of all enzymic activity toward RNA (103). The product has a sedimentation constant and alkaline spectral titration behavior which indicate no marked conformational change. Extensive guanidination can occur with no loss of activity. Only the last one or two groups to be modified are related to the activity loss. Allewell (120) found a residual 1% activity toward C > p after exhaustive reaction of RNase-S. The product was crystallized in a new space group. 

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