SU655307A3 - Method of obtaining guanidine derivatives or salts thereof - Google Patents

Description

(54) METHOD FOR PRODUCING PROIZEYUDNYH GUANIPINOV OR THEIR SALTS 3 piterature described popuchenie derivatives guanitsina by interaction respective apkipizotiomoche wines at elevated temperature and Pressure Research Institute in a polar solvent such as a mixture of water and dimetipformamida, in the presence of a mineral kispoty l, but there are - information about the method of obtaining Gaunidine derivatives of general formula I, possessing valuable properties. The chain of the proposed method 5tp expansion of the range of pharmacologically active compounds, in particular, guanidine derivatives. In accordance with the invention, compounds of the formula I are obtained by the fact that a compound of the formula -C S-R9 where K, I, Rj 6 have the above value and means a carbonyl group by the number of carbon atoms, is reacted with a compound of the formula 111 where 13 5 are as defined above, in the presence of a mineral acid, for example, hydrogen chloride, hydrobromic acid, hydrogen sulfide, or sulfuric acid, in an inert solvent, and melt. The preferred process is carried out in the presence of at least an equivalent amount of a mineral acid, based on the compounds of the formula, however, the compounds of Formula 5 or Y can also be used in a partially non-protonated form. The compounds of formula I may be in the form of free bases or in the form of additive acid cokes. Additive salts of acids, in particular acetates or hydromaleates, can be obtained from free bases in a known manner. The desired products are isolated by known methods in the form of free bases or in the form of salts. Example .1. 1- (5-Chlorindopin-1-ip) -2-cycle lopropi lguani tsin. 074. 1.2 g of cholesterol aa .1 .- (5-chlorinopen-1-yl) -2-methypisothiourea are dissolved in 6 MP of methanol and heated with 15 ml of cyclopropylamine to 1OO C in an autoclave for 5 hours. The reaction solution is evaporated to dryness and extracted with a residue by shaking between ethyl acetate and dilute sodium hydroxide solution. The crude 1- {5-.jatopHHflonHH -1-yl) -2-cyclopropylguanidine, obtained by evaporation of the magnesium sulphate acetic ester solution, is crystallized from ethyl acetate; m.p. 146-.149 ° C. PRI mme R 2. 1-Oxy-2- (indolin-1-yl) guanidine. ; 10 g of 1- {indolin-1-yl) -2-methylisothiourea urea hydrochloride and 11.4 g of hydroxylamine hydrochloride are suspended in 240 mp of ethanol and heated to boiling for 1 hour after the addition of 6.9 g of potassium ethoxide. After cooling, potassium chloride is evaporated and excess hydroxylamine hydrochloride and evaporate the filtrate to dryness. The residue from extraction was extracted by shaking between concentrated aqueous ammonia and methylene chloride. The methylene chloride solution, dried over magnesium sulfate, is evaporated to dryness. The 1-hydroxy-2- (indopin-1-ip) -guanidine obtained in the video residue from evaporation is crystallized after adding acetic acid in the form of acetate from ethanol-ether mixture; m.p. 155-156 C. PRI me R 3. 1l (5-Chlorindolin-1-ip) 2- (2,2-diethoxyethyl) -guanidine. 6 g of hydrochloride 1- (5-chloroindolin-1-ip) -2-methylisothiourea and 1 O ml of aminoacetaldehyde diethyldetal are heated for 1 hour to a bath temperature of 120 ° C. Excess amount of aminoapetaldehyde diethylacetate is evaporated in a vacuum, and the residue is extracted by means of distillation and in a range of 300 h. 1 ". Sodium hydroxide solution. The acetic ether solution, dried over magnesium sulfate, is evaporated to dryness. Obtained as a residue from evaporation of 1- (5-hlorindopiN 1-ip) -2- (2,2-aiethoxyethyl) -guanidine is crystallized as naphthalene -1,5-disulfonate from ethanol-ether mixture, m.p., 163- 165 C. In a similar way, using the corresponding compounds of the formula | in which Nd is methyl, by reacting with the corresponding compounds of the formula, compounds of the formula I are added in the table.

Claims (1)

1. A method for producing guanidine derivatives of the general formula . NH-C K, g -s 3 where R is a hydrogen atom, a radicap with the number of carbon atoms of 1–4 or a fenipap radical in the number of ptomes of carbon 7–9; R, is a hydrogen atom, an off-radical with the number of carbon atoms 1-4, fekilny radical with the number of atoms carbon 7–9 hydroxy group, cycloalkyl radical with carbon number 3–7, phenigenic radical can be replaced by halogen with the sequence number 9-35, a mono- or disubstituted phenipoxyalkyl radical with a carbon number of 8-11, the oxygen atom being separated by at least two carbon atoms. From the nitrogen atom with which dinene radical, aminoalkyl radical with the number of carbon atoms 2-4, which is disubstituted by alkyl groups with the number of carbon atoms 1-4, and the atom. -:, ...,., 1Л. . „.:,; 6 nitrogen is separated by at least two carbon atoms from the nitrogen atom to which the radical is connected, the radical is imip. (Sn), - with that, P means a chain number from 1 to 5 carbon number 1-4; and 4 hydrogen or a radical with 1-4 carbon atoms and T and Rg - independently of one another denote a hydrogen atom or halogen atom with the serial number 9-35, match their sycophants, with the fact that compounds of the general formula -RI . 1 v-ti where R,, Rg and Poison have the indicated values; an alkyl group with 1-4 carbon atoms, is reacted with a compound of the general formula T 2 is as defined above, and the desired products are isolated in a free form or coke. Sources of information taken into account in the examination 1. Patent of the GDR No. 112757 ,. cl. C 07 D 27/72, O9.O7.74.