CS268815B2 - Method of (1-amino-3(/(2-//(diaminomethylene)amino//4-thiazolyl)methyl/-thio)propylidene)sulphuric diamide production - Google Patents

Abstract

1-Amino 3-(((2-((diaminomethylene)amine) 4-thiazolyl) methyl)thio) propylidene, sulphamide is made by reaction of 1-amino 3-(((2-amino 4-thiazolyl) methyl)thio)propylidene sulphamide with a methyl isothiourea salt e.g. sulphate or hydrochloride, in equimolar amt. - Reaction is preformed in a suitable solvent, e.g. a methanol/water mixt. in basic conditions from an aq. soln. of NaOH in molar ratio 2:1 with respect to the methyl isothiourea salt, at 50-80 deg. C. The prod. is isolated and purified by conventional means.

Description

Hg receptors and interesting clinical properties, so it can be used in the treatment of gastric and duodenal ulcers and all other diseases associated with gastric secretion.

Bethylisothioureas of the formula II of the sulfate, hydrochloride, hydrobromide or hydroiodide type and the like in a basic medium in a suitable solvent followed by isolation of the resulting product in a conventional manner.

The reaction can be illustrated by the following scheme:

SCH.

h ₂ Ng-nh (И)

АН

where

АН inorganic acid, such as sulfuric, hydrochloric, bronze, hydroiodic, etc. ·

The reactants are preferably used in a 1: 1 solar ratio, i.e. in stoichiometric amounts.

The process according to the invention is carried out in an organic solvent, for example methanol, ethanol, acetone, or mixtures of these solvents with water.

The process is carried out at temperatures of from 50 to 100 ° C, preferably at the boiling point of the solvent used under reflux.

After completion of the reaction, the desired product is isolated by conventional means and recrystallized from an organic solvent such as ethanol, ethanol and the like to lure the chemically pure resulting 1-amino-3 - [(R 2 -) (diaminomethylene) amino // -4-thlazolyl] ethyl / thio) propylidene sulfamide.

The invention will be illustrated by the following examples:

Example 1 g (0.0755 mol) methylisothiourea sulfate is dissolved in a mixture of 250 ml of water and 100 ml of methanol. The mixture is heated to reflux and 44.5 g (0.151 mol) of 11-amino are added over an hour. -3- [(2-amino) -4-thiazolyl] methyl (thlo) propylidene Jeulfamide (M) in solution in 150 ml of 2 N sodium hydroxide solution. The mixture is heated at reflux for 2 hours, then evaporated to dryness. and

The residue was recrystallized from 80:20 methanol / water lards. The solid was filtered off and washed and recrystallized from ethanol. In this way, a total of 22 g of 1-amino-3- ((R) - [4- (4-thiazolyl) ethyl] thiopropyl-propylenediulfaldehyde was obtained in a white solid in 43% yield.

Mp 162-164 ° C.

The spectrum in the infrared light in the pellet and potassium bromide form is as follows:

3500, 3400, 3370, 3240, 3100, 1635, 1600

1600, 1580, 1530, 1425, 1320, 1290, 1150, 10000, 900, 900, 850, 770 and 680 c · ¹ .

Elemental .C28H28N3O3 _(Bol . _H-rev . _{337> 43)} calculated 28.48% C, 29.06% H, 29.06% I, 28.50% S | Found: C, 28.36; H, 29.18; N, 29.12.

EXAMPLE 2 g (0.0315 mol) of methylisothiourea hydroiodine are dissolved in a mixture of 150 ml of water and 200 ml of methanol. Then, a solution of 9.3 g (0.0315 mol) of 4-amino-3- [beta] -ethanol is added. amino-4-thiazolyl) methyl] thio / propylidene sulfanide and 64 ml of 1N sodium hydroxide are added. The reaction mixture is refluxed for 3 hours. The mixture is then evaporated to aucha to give the crude product which is subjected to a crude product. Chromatographed on a silica gel column, eluting with chloroform / methanol, initially at a ratio of 50 t 1, then gradually changing the ratio up to 40: 10. The fraction and the resulting product was evaporated to dryness, a yield of 34% yields a total of 3.6 g of the resulting .alpha.-amino-3 - ([[2 - [(diaminomethylene) amino] -4-thiezolyl] methyl] thio] propylidene] aa sulfamic, which may be recrystallized from methanol. as the final product, obtained by the method of Ex ladu 1 ·

Claims (5)

SUBJECT OF THE INVENTION A process for the preparation of 1-amino-3 - ([[2- (diealnomethylene) and 1-amino] -4-thiazolyl] ethyl] thiopropylpropylidene sulfamide, characterized in that it is reacted with 1-amino-3- С (2-amino-4-thiazolyl) methylthio / propylidene-4-sulfamide and methylthio-urea salts, such as sulphate · hydrochloride, hydrobromide, hydroiodine from basic conditions in a suitable solvent and subsequent isolation of the resulting product · Process according to Claim 1, characterized in that the es reactants are used in a 1: 1 solar ratio, ie in an etechiomstric amount. Process according to Claims 1 and 2, characterized in that a mixture of methanol and water is used as the reaction medium. 4. A method according to any one of claims 1 to 3, characterized in that a solution of sodium hydroxide in a molar ratio of 2: 1, based on the methylleothiourea salt, is used as the basic medium. 5. A process according to claim 4, wherein the reaction is carried out in a temperature range of 50 to 80 [deg.] C.