SU390718A1 - ALL-UNION - Google Patents

Description

This invention relates to a process for the preparation of novel homoprimidazole derivatives, which have improved medicinal properties and can be used in the pharmaceutical industry.

A method based on the known reaction for the preparation of compounds of the general formula

BI R,

where R is alkyl, alkoxy or halo, RI is hydrogen or halo, Rz is hydrogen, alkyl aralkyl or aryl, H3 is hydrogen, halo, oxymethyl, carboxyl or substituted carboxyl, such as carbalkoxy, R4 is hydrogen, halo, alkoxy -, oxo- or

hydroxy groups ,. Re-alkyl or aralkyl and X-anion.

The method is to connect a common formula.

(where R, RI. Ra, Ra and R4 are as defined above) or its salt, is alkylated or aralkylated, followed by isolation of the target

connections known techniques. For the alkylation reaction can be

for example, alkyl or aralkyl halides are used. The reaction is advisable to carry out

in the presence of an acid binding agent.

Alkylation can be carried out with

using alkyl sulfate, alkyl phosphate, alkyl tosylate or diazomethane. In the above compounds of the first formula

anion X can be exchanged in a known manner for another anion.

Example 1. 116.1 g (0.5 joug) of 3-carbethoxy-4-oxo-6-methylhomopyrimidazole are dissolved in 500 ml of methyl iodide at room temperature. The solution is left to stand in a closed vessel, in a dark place for 5 days at room temperature and with occasional agitation. After 5 days, the precipitated crystals are filtered, washed with a small amount of methanol and dried in air. Obtain 140 g of iodide, 1,6-dimethylZ-carbethoxy-4-oxohomopyrimidazole in the form of yellow crystals, so pl. 230-231 °. The product, recrystallized from a threefold amount of water, has a melting point of pl. 236-237 °. Calculated,%: C 41.72; H 4.04; N 7.48; J 38.91; CnHisNaOsJ. Found,%: C 41.42; H 3.80; N 7.60; J 33.20. Example 2. 2.32 g (0.01 mol) of the base of carboethoxy-4-oxo-6-methylhomonirimidazole is left to stand in 5 ml of methyl bromide acetonium solution (approximately 0.5 gCH3H3O4) for five days at room temperature in the closed vessel in a dark place. The base slowly dissolves and in parallel the reaction product precipitates. Obtain 2.1 g of bromide, 1,6-dimethyl-3 - carbethoxy-4-oxohomopyrimidazole, so pl. 203-204 ° C. It was not possible to recrystallize it. Calculated,%: C47,76; P 4.59; N 8.55; Br 24.45; C.sHisNaOsBr. Paideno,%: C 47.62; H 4.67; N 8.39; Br Example 3. 23.2 g (0.1 mol of 3-carbethoxy-4-oxo-6-methylhomonimryndazole is dissolved in 100 ml of acetone, after which 13.9 g (0.11 mol of dimethyl sulphate (10.5 ml)) are added. Mixture allowed to stand for three days at room temperature with frequent shaking. The precipitated crystals are filtered, washed with acetone and dried to obtain 17 g of methyl sulfate, 1,6-dimethyl-3-carbethoxy-4-oxo-homopyrimidazole, m.p. 177-178 ° C. The product recrystallized from a double amount of alcohol has so that it is 179-180 ° C. It is well soluble in water, calculated: C, 46.85; H, 5.03; N, 7.80; S 8, 92; CuH, 8N207S. Payden o, -%: C, 46.72; P, 4.96; N, 7.68; S, 8.76. Example 4. 17.0 g (0.1 mol of silver nitrate is dissolved in 100 ml of water. With stirring, approximately over a period of 15 minutes, 87.4 g (0.1 mol} of well-triturated 1,6-dimethyl-3-carbethoxy-4-oxo-homopyrimidazole iodide is added to the solution at room temperature, stirred for another hour at room temperature, and then filtered AgJ precipitate and washed with water. The light brown filtrate is evaporated to dryness in a water bath at 60-65 ° under vacuum. Obtain 30 g of light brown crystals, so pl. 170-172 ° C. After two recrystallisations from five times the amount of alcohol, 14 g of 1,6-dimethyl-3-carbethoxy-4-oceanogopyrimidazole nitrate are obtained in the form of needles of a light brown color with a melting point. 176 ° C soluble in water. RP of an aqueous solution of 6-7. Calculated,%: C 50.49; H 4.88; N 13.59; CisnisNsOe. Paydeno,%: C 50.51; P 4.96; N 13.71. The subject of the invention. A process for the preparation of homopyrimidazole derivatives of the general formula: where R is alkyl, alkoxy or halo, RI is hydrogen or halo, R2 is hydrogen, alkyl, aralkyl or aryl, Hz is hydrogen, halo, oxymethyl, carboxyl or substituted carboxyl such as carbalkoxy, R4 is hydrogen, halo, oxo, alkoxy, or hydroxy groups, RS is alkyl or aralkyl and X is an anion, characterized in that the compound of the general formula (where R, Ri, Ra, Rs and R4 have the aforementioned values) or its salt, is alkylated or arylated, and the resulting target compounds are isolated by known techniques.