BACKGROUND OF THE INVENTION : Famotidine is one of the important compounds for the inhibition of gastric and intestinal ulceration. For the preparation of famotidine there are several processes known in the art.

PRIOR ART: EP 0128736 describes the preparation of Famotidine via thiazolin derivatives of formula V The compound of formula V is converted into compound of formula IV, which is a crucial intermediate for the preparation of Famotidine.

Japan Patent application No 53147069 describes the synthesis of famotidine through the intermediate, 2-guanidino-4-chloromethyl thiazole, which is a difficult compound to handle due to its irritable odor. It also causes dermititis.

Hence it was thought worthwhile to achieve a one-pot synthesis of the intermediate of formula IV, which can generate the corresponding mercapto derivative for further synthetic protocol.

OBJECTS OF THE INVENTION : Accordingly, it is the object of the invention to provide an improved process of preparation of Famotidine.

It is an additional object of the invention to provide a one-pot preparation of S- (guanidine-4-yl-methyl)-isothiourea dihydrochloride.

SUMMARY OF THE INVENTION: The invention relates to a new process for one pot preparation of S-- (Guanidino-4-yl methyl)-isothiourea dihydrochloride of formula IV, in a crucial intermediate for the synthesis of the anti-ulcer drug famotidine, by the reaction of amidino thiourea of the formula 11 with 1, 3-dichloro acetone of formula I in acetone containing potassium iodide to give

2-guanidino thiazole-4-methyl chloride hydrochloride of formula III and reacting the intermediate with thiourea in the presence of acetic acid to furnish the compound of formula IV in excellent yield.

DESCRIPTION OF THE INVENTION The reaction of 1, 3-dichloro acetone of formula I with gunadinothiourea of formula-il was tried in different solvents like alkanones, alkyl nitriles and more polar solvents like dimethyl formamide. The observation was that alkanones, which are of moderate polarity, gave better output of the intermediate compound of formula Ill. Among the alkanones, 2-propanone was found to be more preferable. The reaction in 2- proponone was studied at temperature range of 0°C to 30°C. A temperature range of 10° C to 15°C was more preferable, since at 0°C the formation of the first stage <BR> <BR> product was very slow viz. , around 48 hours and at 10° C to 15°C the duration was 4 to 5 hours. The presence of an alkali iodide like potassium iodide or sodium iodide resulted in a better yield of the intermediate product (formula 111) Potassium iodide was found to be more preferable.

In the initial experiments, the intermediate of formula III was isolated and then converted into the compound of formula IV. The yield for the intermediate of formula III was about 90-93%. The conversion of the intermediate of formula III to <BR> <BR> intermediate of formula IV was tried in different alkanols viz. , methanol, ethanol, n- proponal, isoproponal etc. It was most preferable to use isoproponal, since this

solvent gave the best results. The compound of formula IV was isolated in about 83% yield.

Since it was difficult to handle the intermediate compound of formula III, it was thought worthwhile to attempt a one-pot process. On completion of the first stage of the reaction, thiourea was added to the reaction mixture and the reaction was continued in order to form the compound of formula IV. In 2-propanone alone, the reaction did not proceed further.

It was decided to add a co-solvent for the second phase of the reaction. Alkanols like methanol, n-proponal, isoproponal, etc in different proportions (5-25%) and at different reaction temperatures (25-50°C) were tried. In a solvent like methanol the yield was less (around 40%) and in a solvent like isopropyl alcohol the yield was moderate (around 65-75%). Solvents like dimethyl formamide, dimethyl sulphoxide as co- solvents did not give good yields. When the reaction was tried using alkane carboxylic acid as a co-solvent, it gave excellent results. Ethanoic acid was found to be the most preferred choice. The concentration of ethanoic acid was preferable in the range to 10 to 30%. It was more preferable to have ethanoic acid concentration in the range of 15-20%. A temperature range of 30-50°C was preferred for the reaction.

A temperature range of 35°-45° C was more preferred. The overall yield of the compound IV was around 92-93%.

The following experiments illustrate the invention.

EXAMPLE-I One pot preparation of N- [4-(amino iminoethyl) thio] methyl]-2-thiozolyl]- guanidine dihydrochloride 150kg of 1,3 dichloroacetone and 6.75 kg potassium iodide was charged in 2KL GLR containing 7501ts of acetone (2-propanone). The mixture was cooled under stirring to

a temperature of 10-15°C. To this reaction mixture guanidino thiourea (141 kg) was charged in instalments maintaining the reaction temperature at 10-12°C. The duration of the addition was 4-5hours. After the addition, the reaction mixture was stirred at 10-12° C for another hour. The reaction mass was allowed to warm to about 25°-30° C and ethanoic acid (144kg) was charged into the reactor in about 30min. Then the reaction mass was warmed to 40° C under stirring and thiourea (90kg) was charged.

After charging thiourea, the reaction mass was heated to reflux temperature and maintained for 4-5hours. Then the reaction mass was cooled to 10° C and the precipitated product was centrifuged. The cake was washed with isopropyl alcohol (2 x 901ts). The product was dried at 75°-80° C to yield 330 kg of the dihydrochloride with melting point of 205-210°C EXAMPLE-II a) Preparation of 2-guanidino-4-thiozole methyl chloride hydrochloride In a 2KL GLR, àcetone (7501ts) was charged and cooled to 10°-15° C. 1,3 dichloroacetone (150kg) and potassium iodide (6.75kg) was charged into the reactor.

To this reaction mixture under stirring, 141 kg of gunadinothiourea was charged maintaining the temperature at 10°-12° C. The addition took about 4-5hours. After the addition, the reaction mixture was stirred at 10°-12° C for one hour and the precipitated cake was centrifuged. The cake was washed with cold acetone (2 x 50its), spin dried, and dried at 75°-80° C to yield 250 kg of the title product with the melting point of 185-190°C b) Preparation of N-[[4-(amino iminoethyl) thio] methyl]-2-thiozolyll-guanidine dihydrochloride In a 2KL GLR, isopropyl alcohol was charged. The product obtained in the earlier experiment (II a, 250 kgs) and thiourea (86kg) were charged into the reactor and the mixture was heated to around 70°C and maintained at 70°-75° C for one hour. The

reaction mass was cooled to about 25° C and then centrifuged. The mass was washed with isopropyl alcohol (2 x 601ts) and spin-dried to yield around 300kg of the title product with melting point of 205-210°C