DE2008875A1 - Pyrimidine derivatives - Google Patents

Description

Folder 22192 - Dr.K.
Case D.21741

IMPERIAL CHEMICAL INDUSTRIES LTD. London, UK

Pyrimidine derivatives

Priority: February 26, 1969 - Great Britain

The invention relates to pyrimidine derivatives and in particular on new 2-alkoxy-4-hydroxypyrisidines and the salts the same.

According to de? Invention are new 2-alkoxy- ^ b ^ droxypyriaddine the formula

00983T / 2238

where B is an alkyl group having 1-6 carbon atoms and lc and Rg (which can be the same or different) Alky.Lgruppen Bit 1-8 mean carbon atoms, as well as the Salts of the same suggested.

According to the invention, a method for preparing said continues to 2-alkoxy-4-hydroxypyrimidines or the salts thereof, _t proposed which is carried out by one Dafi an O-alkyl-isoharnetoff the formula in the presence of a base with a beta-keto ester

IF

1 1 of the formula RgCO-CH-COOH, where H is an alkyl group with

1-3 carbon atoms and preferably an ethyl group means and H, Rr and Rg have the above definitions, implements.

The reaction is conveniently carried out so that the O-alkylisourea is used in the form of a salt, for example in the form of the hydrochloride, but other salts such as the sulphate or the p-toluenesulphonate can also be used.

Ss can be a wide range of inorganic and organic Bases can be used in the reaction, such as alkali metal or alkaline earth metal hydroxides, alkoxides, carbonates or acetates, organic amines or quaternary ammonium hydroxides. The use of an alkali metal hydroxide or Alkoxide is particularly preferred. Thus, the reaction can be carried out by adding a solution of the O-alkylisohamea in an alkanol (for example methanol) with converts the beta-ketoester in the presence of sodium or potassium into an alkanol (for example methanol). Preferably an excess of the O-alkylisourea is used.

00983772238 bad original

The reaction is preferably carried out at room temperature a period of 10-30 hours (for example 20 hours " followed by refluxing.

The free 2-Alko: xy-4-hydroxypyriaidin can be acidified of the salt formed can be set free. A wide range of salts can be used, for example alkali metal or alkaline earth metal salts, salts of organic amines or quaternary ammonium salts, if the appropriate base is used in the above reaction or if, for example, the free 2-alkoxy-4-hydroxypyriaidin is used neutralized by double implementation.

The mentioned 2-alkoxy-4-hydro3grpyrimidines or the salts dertelben can, for example, in the corresponding 2-Alkylamino - ^ - hydroxypyriBiidine or in the salts or Ether of the same transformed - «to earth. The usage of 2-A2kylamino-4-hydroxy-5,6-dialkylpyrimidines (and the String and its ether) in fungoid compositions is in British patent specification 1,182,584 and in the South African patent 1130/68.

The process described here is particularly focused on the production Clay 2-alkoxy-4-hydroxypyrimidines of the general Fore el I applicable, where H, H, - and Rg (which are the same or can be different) alkyl groups with 1-4 carbon atoms are such as 2-MBtIiOXy-A-hydroxy-5-n-butyl-6-methylpyriatidine (and its salts). These alkoxy derivatives can then, for example, be converted into the alkylamino derivatives Fontel

Ηβ-ΥΥΟΗ

009837/2238

where R ^ is hydrogen or an alkyl group with 1-4 carbon atoms, R _{2 is} an alkyl group with Ί-4 carbon atoms and R, - and R ^ have the above definitions (for example 2-dimethylamino-4-hydroxy-5- n-butyl-6-methylpyrimidine and 2-ithylamino-4-hydroxy-5-n-butyl-6-methylpyrimidine).

Conversion of the 2-alkoxy-4-hydroxy-5,6-dialkylpyrimidines (or the salts thereof) into the corresponding 2-alkylamino-4-hydroxy-5,6-dialkylpyrimidines (or the salts thereof) is expediently carried out by that, for example, the 2-alkoxy derivative is reacted with the corresponding amine. Ss can either be the free amine or an amine salt (e.g. the acetate) can be used.

The amination can conveniently be carried out using either water or a lower alkanol or a mixture of the two as solvent. In this case one preferably operates at an elevated temperature, for example 80-180 ⁰ C, in a closed container the autogenous pressure un ter the reaction.

The invention is illustrated in more detail by the following examples.

example 1

An odor of 470 g of ethyl-n-butyl acetoacetate and a solution of 2Θ80 g of O-methyl-iaourea hydrochloride in 10 1 of methanol was gradually added over a period of 1 hour to a stirred solution of 905 g of sodium in 10 1 of methanol. The resulting mixture was for 20 hours at room temperature (20 ⁰ C) was allowed to stand, after which it was stirred for 1 hour and heated to reflux. The mixture was then distilled off and the residue was dissolved in 20 liters of water. The solution was made by adding hydrochloric acid

009837/2238 bathroom ORIGINAL

acidified to pH 6-7. The solution obtained in this way was filtered off, washed with water and dried, leaving 2240 g of 2-methoxy-4-hydroxy-5-n-butyl-6-methylpyrimidine (61% yield).

The 2-methoxy derivative obtained in this way was mixed with 3210 g of an aqueous solution of monoethylamine (containing 70% by weight of monoethylamine) and 10 l of methanol. ^{The mixture was heated to 100 °} C. for 2 hours under autogenous pressure in a closed container. The methanol and excess ethylamine were distilled off and the residue was mixed with 10 l of water. The solid thus obtained was filtered, washed with water and dried to give 2240 g of 2-lthylamino-4-hydroxy-5-n-butyl-6-metl: were obtained o ^r l ~ pyrimldin (melting point 156-158 ° C ; 94% yield).

Example 2

The procedure described in Example 1 was repeated with the difference that the amination was carried out as follows became:

The 2-methoxy derivative was mixed with 5140 g of an aqueous solution of monoethylamine (containing 70% by weight of monoethylamine) and 4800 g of glacial acetic acid. The mixture was heated, and the water was distilled off until the temperature of the Gbemische rose to 140 ⁰ C. The temperature was maintained for 2 hours at 140-145 ⁰ C .. 5 1 of water were then added. The thus obtained pesticide was filtered off, washed with water and dried to obtain 2240 g of 2-ethylamino-4-hydroxy-5-n- "butyl-6-methylpyrimidine (94% yield).

BATH 009837/2238

Claims (6)

Claims *. 2-alkoxy-4-hydroxypyrimidines of the formula where R is an alkyl group with 1-8 carbon atoms and Rc and Rg (which can be the same or different) Mean alkyl groups with 1-8 carbon atoms, as well as the Salts of the same. 2. A compound according to claim 1, characterized in that net that E, Rr and Rg (which are the same or different can be) denote alkyl groups with 1-4 carbon atoms. 3 · 2-Methoxy-4 · -hydroxy-5-n-butyl-6-methoxy pyrimide in or the Salts of the same. 4 ·. Process for the preparation of the compounds according to one of Claims 1 to 3 »characterized in that an O-alkyliaourea of the formula H ₂ NC-NH OH in the presence of a baae with a beta-ketoeoter of the formula 1 1
R ₆ OO-CH-COOR, where R is an alkyl group with 1-8 carbon atoms "means converts. BATH ORIGINAL 009837/2238 5. The method according to claim 4, characterized net gekennzeich that R is a ithylgruppe. 6. The method according to claim 4 or 5. characterized g β k β η η - »eichnet that the base let an alkali metal hydroxide or alkoxide. M-INO H HNCItE. DI ING H BOHi Din ING. S S ^- AEGEI BATH 009837/2231