DE888542C - Process for the preparation of 4-amino-5-arylpyrimidine compounds optionally substituted in the 2- and / or 6-position - Google Patents

Description

Process for the production of optionally in the 2- and / or 6-position substituted 4-amino-5-arylpyrimidine derivatives The invention relates to a new process for the production of optionally in the 2- and / or 6-position substituted 4-amino-5-arylpyrimidines, including 2,4-diamino-5-aryl-pyrimidines, z. B. 2, q.-Diamino-5-p-chlorophenyl-pyrimidine, which previously only on more complicated Paths could be established. Even more important, however, is the fact that the new methods a large number of substances, e.g. B. the 2,4-diamino-5-phenyl-6-alkylpyrimidines, makes accessible which so far not at all after those known in the art Process could be produced.

The process according to the invention consists in the ring-closing condensation of a ß-alkoxymethylene-arylacetonitrile (I) (which substances can also be referred to as a-alkoxymethylene-arylacetonitrile) with a suitable Ham $ toffderivat (II), z. B. guanidine (X = NH,) and amidines (X = H, alkyl or aryl) to give 2,6-di-substituted-q.-amino-5-arylpyrimidines (III). This reaction can be expressed by the following general formula to be announced in more detail. - In this formula, X is hydrogen or an amino, alkyl or aryl radical, Ar is an aryl radical which can be substituted, R is hydrogen or an -aryl: or -alkyl radical; each of which may be substituted and R 'is an alkyl group. The range of this reaction is illustrated in more detail by the following examples.-The essence of the invention is the finding that, while the ß-oxy-a-arylacrylonitrile (which can also be called a-acylacetonitrile, since the two forms are tautomeric) with condense the urea derivatives very poorly or do not react with them at all, condense the corresponding alkoxy derivatives (β-alkoxy-a-arylacrylonitriles) smoothly, in order to give the desired pyrimidirism in good yield. For the purposes of this process it is not necessary to extract the alkoxy derivative serving as the output compound from its origin. to be separated in a mixed position, and "for the sake of convenience it is usually omitted. It is often preferred to carry out the alkylation with diazomihan in an ethereal solution, to evaporate the ether and - without further purification - to convert the product with a functional urea derivative of the specified composition. Since the alkyl group R '. is split off when the gyrimidine ring is closed, its nature is not important for the reaction. All low molecular weight alkyl groups are considered equivalent; the preference of one or the other of these is dictated only by reasons of convenience and availability.

As indicated below, it is preferred to prepare the β-alkoxy-α-arylacrylonitriles (VIII) from the corresponding oxy derivatives (VII), although in some cases the alkoxy derivative can be obtained directly from the arylacetonitriles. The arylacetonitriles (V) are expediently synthesized from arylmethyl halides .. (IV) by reacting them with alkali metal cyanides. The a-oxy derivatives (VII) can be prepared by reacting the arylacetonitriles with the suitable esters (VI) in the presence of an alkali metal alcoholate. These reactions are shown in the following formulas The ß-alkoxy-a-arylacetonitriles (VIII) can be prepared from the u-acylarylacetonitriles in the most varied of ways. However, the use of common alkylating agents, e.g. B. the alkyl halides and dialkyl sulfates, usually only a lower yield in the pyrimidine ring closure. The preferred method of making the β-alkoxy-α-arylacrylonitrile is by treating the acyl derivative with diazomethane to produce the β-methoxy-α-arylacrylonitrile.

It was found that by the method according to the invention manufacturable products versatile and useful application in. the pharmaceutical Industry can find. It was found that representatives of this group had a have antibacterial activity and useful pharmacological properties; so, as has been established, individual representatives have, which will be discussed in more detail below be defined, _- an excellent effect against malaria. Likewise are the compounds are useful intermediates in the manufacture of pharmaceutical Preparations and in veterinary medicine.

A class of compounds which has made the process according to the invention more accessible than has hitherto been the case; and which have been found to have excellent anti-malarial activity are compounds of the general formula wherein Y is a halogen atom or a nitro group and R2 is hydrogen or an alkyl radical time z to q. Is carbon atoms. The compound ä, q.-Diamino-5-p-chlorophenyl-6-ethylpyrimidine is particularly valuable.

Another group of compounds of considerable activity against malaria are compounds of the general formula (X) -in which R2 has the same meaning as before, Z is a -halogen atom and W is hydrogen or a halogen atom. Compounds of the formulas (IX) and (X) can be presented and administered as salts of acids which are non-toxic at the dosage at which the drugs are administered.

The invention therefore includes both a process for the preparation of [-Amino-5-aryl-pyrimidines by reacting an a-aryl-ß-alkoxy-acrylonitrile with Guanidine or an amidine as well as the preparation of compounds of general Formulas (IX) or (X) or their salts as valuable compounds which have an effect against malaria.

The invention is now illustrated in more detail by the following examples illustrated. Example r 2, 4-diamino-5-phenyl-pyrimidine from α-formyla-phenylacetonitrile and guanidine The importance of O-alkylation and the use of various Alkylating agents in the production of ß-alkoxy-a-phenyl-acrylonitrile can be such as illustrated below.

Guanidine (from guanidine hydrochloride and sodium ethylate) was heated in alcoholic solution with α-formyla-phenylacetonitrile, and the reaction products of the latter were treated with various alkylating agents on a reflux condenser for 3 to 6 hours. The 2,4-diamino-5-phenyl-pyrimidine was separated off and weighed. Alkyher Yield of 2, q-diamino 5-phenyl-pyrimidine None. . .. .. ... . ... . . Insignificant Dimethyl sulfate. . . . . . . . . . 5 "/ 0 Methyl iodide ............ = Z 0/0 Ethyl bromide. . . . . . . . . . . . 13.511 / 0 Diazomethane ........... 6o 0/0 Example 2 2, 4-diamino-5-p-chlorophenyl-6-methyl-pyrimidine The direct condensation of guanidine with ap-chlorophenylacetonitrile or with a-acetyl-p-chlorophenyl acetic acid ethyl ester; failed and gave neither the 2,4-diamino- nor the 2-amino-4-oxy-pyrimidine in any appreciable amount.

α-Acetyl-p-chlorophenylacetonitrile (g, 7 g) was treated with diazomethane (from zo g nitrosomethylurea) in ether (250 cm3). After standing overnight at room temperature, the ether was evaporated and replaced by absolute ethanol (50 cm3). A solution of guanidine (from 4.6 g of guanidine hydrochloride and 1.2 g of sodium in 50 cm 3 of alcohol) was added to this, and the mixture was refluxed on the steam bath for 12 hours. The alcohol was evaporated, 5N sodium hydroxide solution was added and the mixture was filtered. The residue was purified by dissolving in dilute aqueous acetic acid, treating with charcoal and reprecipitation with sodium hydroxide. After recrystallization from aqueous ethanol, the 2, [-diamino-5-p-chlorophenyl-6-methyl-pyrimidine melted at 26 [to] 265 '. Yield about 60 "/ ,.

The same compound was made in the same way by condensation of guanidine with ß-ethoxyß-methyl-a-p-chlorophenylacrylonitrile (a- [methylethoxymethylene] -p-chlorophenylacetonitrile) manufactured. After cleaning as before, the compound melted at 264-265 '. the Yield was about 70% based on α-formyl-p-chlorophenylacetonitrile.

Example 3 Preparation of 2,4-diamino-5-p-chlorophenyl-6-ethyl-pyrimidine a-propionyl-ap-chlorophenylacetonitrile p-Chlorophenylacetonitrile (36.5 g) and ethyl propionate (25.5 g) were added to a solution of sodium ethylate (from 5.75 g of sodium) in absolute ethanol (150 cm3). The solution was heated on a steam bath for 6 hours. After cooling, the whole was poured into water and the oil was extracted well with ether, the ethereal solution was removed and the aqueous solution was neutralized with n-sulfuric acid. A heavy oil separated out, which was taken up in ether, washed with water, then with bicarbonate solution and again with water. After drying, the ether was removed and a thick oil (3q., 6 g) resulted which solidified on standing. After recrystallization from a mixture of ether and petroleum ether, it formed needles with a melting point of ro8 to 112 '(6.5% N were found, while the compound C11HloONCI requires 6.7% N).

The above keto-nitrile (i5 g) was with. Diazomethane methylated in ether. (The diazomethane solution was prepared from N-nitrosomethyl urea (20 g) as previously described). Ether and excess diazomethane were evaporated on the steam bath and the oil was dissolved in ethanol (50 cm3). To this end, a solution of guanidine in ethanol too cm3 (made from 8.1 g of the hydrochloride) was added. The solution was refluxed for 5 hours, the alcohol removed and the residue treated with 5N sodium hydroxide. The insoluble material was then filtered off. After purification by precipitation from dilute acetic acid with sodium hydroxide and by recrystallization from ethanol, the product formed clear, colorless needles (8.0 g) with a melting point of 218 to 22o '. (Found 58.0% C; 5.1% H, 22.10 / 0 N. Compound C "H" N, C1 requires 57.9 0/0 C, 5.2 0 / (, H and 22 , 5% N.) Example 4 2,4-Diamino-5-p-chlorophenyl-6-n-propyl-pyrimidine This compound was prepared exactly as above from β-methoxy β-n-propyl-ap-chlorophenylacrylonitrile it was obtained in 56% yield, and after recrystallization from alcohol it melted at 171 to z74 °.

Example 5 2,4-Diamino-5-p-chlorophenyl-6-isobutyl-pyrimidine These The compound was made from ß-methoxy = ß-isobutyl-a-p-chlorophenylacrylonitrile as before manufactured. Crystallized from benzene, it formed colorless prisms with a melting point from 147 to i48 °. Example 6 2,4-Diamino-5-p-chlorophenyl-6-a-ethyl-n-propylpyrimidine This compound was prepared from the corresponding ketonitrile as above. the end Benzene petroleum ether crystallized colorless prisms with a melting point of 225 to 228 °. Example 7 2,4-Diamino-5-phenyl-6-methyl-pyrimidine The direct Condensation of guanidine with a-acetyl-a-phenylacetonitrile and with a-acetylphenyl acetic acid ethyl ester failed and gave neither the 2,4-diamino nor the 2-amino-4-oxy-pyrimidine derivative in significant quantities.

A solution of ß-methyl ß-methoxy-a-phenylacrylonitrile (8, o g) (from a-acetyl-a-phenylacetonitrile and diazomethane as in example 2) in zoo cms ethanol was treated with a solution of guanidine (from 4.5 g of the hydrochloride and 1.2 g of sodium in 10 cm3 of ethanol), and the mixture was left on the steam bath for 16 hours heated. The alcohol was evaporated and the solids were, after Treatment with concentrated sodium hydroxide solution, filtered off. The connection was made by dissolving in aqueous acetic acid, and finally precipitating with sodium hydroxide purified by recrystallization from aqueous ethanol. The product (5.3 g) melted at 249 to 251 °.

The same compound was obtained from the condensation of β-methyl ß-benzyloxy-a-phenylacrylonitrile with guanidine. Example 8 2,4-Diamino-5-p-nitrophenyl-6-methylpyrimidine The pyrimidine derivative prepared according to Example 7 (5 g) was concentrated in Sulfuric acid (40 cm3) dissolved and the solution cooled to -5 °. With cooling and stirring the solution was given potassium nitrate (2.5 g) in small aliquots during the course added from about 1 hour. After another hour in the cold it became Pour mixture over crushed ice and make alkaline with sodium hydroxide. After cleaning it was found that the product decomposed at over 35o °, but did not melt (Analysis N calculated: 27.5%, found: 28, o Example 9 2,4-Diamino-5-p-chlorophenyl-6-n-amyl-pyrimidine The condensation of ß-n-amyl-ß-methoxy-a-pchlorophenylacrylonitrile (0.05 mol) and guanidine (from guanidine hydrochloride and sodium in alcohol; o, o5 mol) in alcoholic solution as above gave 2,4-diamino-5-p-chlorophenyl-6-n-amylpyrimidine in about 70% yield, based on the keto-nitrile. Crystallize after Uml @ from ethanol the product formed colorless needles with a melting point of 188 bis 19o °. Example 1o 2, 4-Diamino-5-p-chlorophenyl-6-n-undecylpyrimidine a-Lauryl-a-p-chlorophenylacetonitrile was treated with diazomethane in essential solution and the product was accurate like the corresponding acetyl derivative in Example 2 condensed with guanidine. That Material was separated after extraction with sodium hydroxide solution and from methanol recrystallized with a content of 10% benzene. It made slide with one Melting point from 139 to 14o °. The yield calculated from the α-acylphenyl-acetonitrile amounted to more than 6o%. Example 11 2,4-Diamino-5-p-chlorophenyl-6 ß-phenylethylpyrimidine This compound was prepared as described above from ß-methoxy-ß-phenylethyl-a-p-chlorophenylacrvlnitril and guanidine. It was cleaned in the usual way and made from methanol recrystallized. It formed needles with a melting point of 15o to 154 °. example 12 2,4-Diamino-5-phenyl-6- (N-methyl-N-phenylaminomethyl) -pyrimidine phenylacetonitrile was with N-phenyl-N-methylglycine ester in alcoholic solution with 1 mol of sodium ethylate condensed. The product was treated with diazomethane in an ethereal solution and condensed without further purification with guanidine in alcoholic solution. The product was cleaned in the usual way and from a mixture of benzene and petroleum ether recrystallized. It melted at 150-152 ° and was in about 50% yield obtain.

Example 13 2,4-Diamino-5-o-chlorophenyl-pyrimidine Neither α-formyl-α-o-chlorophenylacetonitrile still a-formyl-a-o-chlorophenylacetic acid ethyl ester condensed with Guanidine so that they would have given a pyrimidine derivative in any appreciable amount.

When the formyl nitrile is treated with diazomethane as described above and then condensed with guanidine in the usual manner, one obtained good yield of 2, 4-diamino-5-o-chlorophenylpyrimidine with a melting point of reg to z31 °. Example 14 2,4-Diamino-5-a-naphthyl-6-methyl-pyrimidine This derivative was made from ß-methoxy ß-methyla-i-naphthyl-acrylonitrile and guanidine. It melted after recrystallization from benzene at 159 to 16o0. Example 15 2,4-Diamino-5-a-naphthyl-pyrimidine By methylation of a-formyl-a-naphthylacetonitrile with diazomethane and condensation of the product with guanidine in alcoholic solution, 2,4-diamino-5-a-naphthyl-pyrimidine was obtained in very high yield. After recrystallization from a mixture of benzene and Petroleum ether formed needles with a melting point of 179 to 180 °. example 16 2,4-Diamino-5-p-chlorophenyl-6-phenyl-pyrimidine ethyl benzoate was treated with p-chlorophenylacetonitrile condensed in the presence of sodium ethylate. The a-Benzoyl-a-p-chlorophenylacetoacetate was treated with diazomethane in ethereal solution and the product was with Guanidine condensed in alcoholic solution. The product was in the usual Way purified and recrystallized from ethanol; it melted at 268 to 27o0. example 17 2, 4-diamino-5, 6-diphenyl-pyrimidine a) a-Benzoyl-a-phenylacetonitrile (cyandesoxybenzoin) was in alcoholic solution under reflux for 16 hours with 1 mole of guanidine heated. The alcohol was evaporated and the residue was concentrated with Sodium hydroxide solution and treated by dissolving in aqueous acetic acid and precipitating cleaned with sodium hydroxide. The small residue decomposed in the range of 24o to 300 °. Recrystallization from ethyl alcohol gave a small amount of Material with a melting point of 133 to 134 °.

b) The repetition of the above experiment resulted in a small amount of Material with a melting point of 227 to 235 °.

The investigation of the ultraviolet absorption spectra according to a) and b) products obtained showed the absence of 2, 4-diamino-5, 6-diphenyl-pyrimidine, of which an authentic pattern, as described below under c), is produced became.

c) Cyandesoxybenzoin was treated with diazomethane in the usual way. After the ether and excess diazomethane had evaporated, an alcoholic solution of guanidine was added and the mixture was heated on the steam bath for 4 hours. The resulting solution was evaporated and the residue was worked up in the usual manner. After recrystallization from ethanol, the 2,4-diamino-5, 6-diphenyl-pyrimidine melted at 241 to 242 °. The ultravilet absorption spectrum. agreed with the predicted structure. With a pii value of i, o: minimum 268 mu, E; m 186o; Maximum 292.5 mu, E '1m 258o; at a pH value of ii, o: maximum 238 mu, E; m 545o; Minimum 28o mu, E; m 165o; Max 300 mft, E; m 2420 example ate 4-amino-5-phenyl-pyrimidine A mixture of approximately equimolecular proportions of ß-methoxy-a-phenylacrylonitrile and formamidine (from the hydrochloride with sodium in alcohol) in alcoholic solution was refluxed for 4 hours, the Solution evaporated and the residue, after extracting with sodium hydroxide solution, dissolved in aqueous acetic acid and reprecipitated with sodium hydroxide. After recrystallization from benzene, the product was obtained as a platelet with a melting point of 152 to 1550; it was identical to an authentic sample made by the Davies and Johnson method (U.S. Patent 2,418,548). Example ig 4-Amino-6-methyl-5-phenyl-pyrimidine The condensation of ß-methoxy-p-methyl-a-phenylacrylonitrile with formamidine was carried out by heating an alcoholic solution of approximately equimolecular amounts of both on the reflux condenser for 12 hours. The product was isolated as described above and recrystallized from benzene. Melting point 174 to 1760. 'Example 2o 4-Amino-5-p-chlorophenyl-6-phenyl-pyrimidine Formamidine was in alcoholic solution with an approximately equimolecular amount of ß-phenylß-methoxy-ap-chlorophenylacrylonitrile (from a-benzoylp- chlorophenylacetonitrile and excess diazomethanine ether) heated for 6 hours. The product was worked up as in Example 17 and recrystallized from benzene. Melting point 225 to 2270. Example 2i 4-Amino-2-methyl-5-p-chlorophenyl-pyrimidine This substance was obtained by the condensation of approximately equimolecular amounts of ß-ethoxy-ap-chlorophenylacrylonitrile and acetamidine (from the hydrochloride with sodium in alcohol) manufactured. The product was worked up as before and recrystallized from aqueous ethanol; it melted at 177 to 17g0. Example 22 4-Amino-5-p-chlorophenyl-2,6-dimethyl-pyrimidine This compound was prepared, as in the previous example, by the condensation of β-methoxy-β-methyl-ap-chlorophenylacrylonitrile with acetamidine. It was recrystallized from a mixture of benzene and petroleum ether and then melted at toi to 2o2 °. Example 23 4-Amino-5-p-chlorophenyl-2-methyl-6-phenylpyrimidine α-Benzoyl-p-chlorophenylacetonitrile was treated with a slight excess of diazomethane in an ethereal solution. After evaporation of the ether, alcohol and an alcoholic solution of acetamidine (from the alcoholic solution of the hydrochloride by adding a solution of an equivalent amount of sodium in absolute ethanol) were added. The mixture was refluxed. Heated for 7 hours, the alcohol was evaporated, and the product would be worked up in the usual way. It was recrystallized from a mixture of benzene and alcohol, and melted at toi to 2o2 °. Example 24 4-Amino-5-p-chlorophenyl-2-p-tolyl-pyriinidine The condensation of β-methoxy-ap-chlorophenylacrylonitrile and p-toluamidine was carried out in an alcoholic solution by heating for 6 hours on the steam bath. The product. was worked up in the usual way and gave light yellow prisms with a melting point of 185 to 187 °. Example 25 4-Amino-5-p-chlorophenyl-6-methyl-2-phenylpyrimidine The methylation of a-acetyl-p-chlorophenylacetonitrile with. Diazomethane gave ß-methoxy-ß-methyla-p-chlorophenylacrylonitrile, which was condensed with benzaniidine in the usual way to give 4-amino-5 = p-chlorophenyl-6-methyl-2-phenyl-pyrimidine, which as in the above examples and was recrystallized from benzene. Melting point 154-155 °. Example 26 4-Amino-5-p-chlorophenyl-6-phenyl-2-p-tolylpyrimidine The above compound was prepared by treating α-benzoyl-ap-chlorophenylacetonitrile with diazomethane and reacting the product thus obtained in alcohol in an approximately equimolecular amount prepared by refluxing p-toluamidine for 6 hours. After evaporation of the alcohol and extraction of the residue with sodium hydroxide solution, the substance was recrystallized from benzene. Melting point 245 to 247 °. Example 27 2,4-Diamino-5-p-chlorophenyl-6-n-butyl-pyrimidine The condensation of β-methoxy-β-n-butyl-α-pchlorophenylacrylonitrile with guanidine as described above gave 2,4-diamino -5-p-chlorophenyl-6-n-butyl-pyrimidine in good yield. After recrystallization from aqueous ethanol, the compound melted at 2o8 to 2io °. Example 28 2,4-diamino-5-p-nitrophenyl-6-ethyl-pyrimidine This compound was prepared by nitrating 2,4-diamino-5-phenyl-6-ethyl-pyrimidine. The latter was produced and nitrided analogously to the operations described in Examples 7 and 8. The product was crystallized by dissolving in 50% alcohol with a slight excess of lactic acid and precipitating on addition of sodium hydroxide solution. When heated to 300 ° it did not melt. Example 29 2,4-diamino-5-p-bromophenyl-6-ethyl-pyrimidine The condensation of ß-ethyl ß-ethoxy-ap-bromophenylacrylonitrile and guanidine gave 2,4-diamino-5-p-bromophenyl-pyrinidine in good condition Yield. The compound was purified according to the procedure described in Example 2. Melting point 213 to 26 °. Example 30 A. m-Fluorophenylacetonitrile m-Fluorotoluene (55 g) was refluxed with sulfuryl chloride (67.5 g) in the presence of benzoyl peroxide (0.5 g). When the evolution of hydrogen chloride had ceased, the oil was washed out once with water and then refluxed with potassium cyanide (42 g) in ethanol (100 cm 3) and water (50 cm 3) for 10 hours. The mixture was poured into water, the oil was extracted with ether and washed well with water. During the distillation it boiled at Kplo 124 to 126 °; Yield 28g. B. α-Acetyl-am-fluoroacetonitrile The above nitrile (13.5 g) and ethyl acetate (8.8 g) were added to a solution of sodium (2.3 g) in ethanol (30 cm3). The mixture was heated for 5 hours. The whole was then poured into water, any oily substance that had separated out was removed with ether and the aqueous solution was acidified with i nH, S 04. The keto-nitrile was separated off and recrystallized from ether (petroleum ether) as needles with a melting point of 117 to 120 °. C. 2,4-Diamino-5-m-fluorophenyl-6-methyl-pyrimidine The above ketonitrile (7 g) was treated with diazomethane (from 10 g of nitrosomethylurea) in ether. The ether was removed and the product which remained as a residue was treated with guanidine (1 mol) in alcohol. After heating on a steam bath for 3 hours, the alcohol was evaporated and concentrated sodium hydroxide was added. The product was filtered off and recrystallized from ethanol water. Melting point 237 to 238 °; Yield 3, o g.

Calculated for C11H11N.F: 6o, 5% C, 5, o% H. Found: 6o, 2% C, 5.2 % H. Example 31 2,4-Diamino-5-m-chlorophenyl-6-methyl-pyrimidine α-acetyl-α-m-chlorophenylacetonitrile (9.7 g) was reacted with diazomethane to give a-m-chlorophenylß-methoxy ß-methylacrylonitrile to surrender. This was then made with guanidine (from 4.7 g of the hydrochloride) in ethanol implemented. The product was worked up as in the previous examples. After recrystallizing from ethanol, it melted at 21-220F.

Calculated for C11H11N4C1: 24.1% N. Found: 23.9% N.

Example 32 2,4-Diamino-5-m-bromophenyl-6-methyl-pyrimidine Prepared from α-acetyl-m-bromophenylacetonitrile as above. After recrystallization from ethanol water the product melted at 235 to 237 '. Example 33.

2, 4-diamino-5- (3 ', 4'-dichlorophenyl) -6-methylpyrimidine a-acetyl-a-3', 4'-dichlorophenylacetonitrile (melting point: Ist to I63 ') (I1.4 g) was treated with methyl orthoacetate (25 cm3) heated. The low boiling point products were used throughout Time of their formation away. Then the orthoester was distilled in vacuo removed. The product solidified and formed platelets when recrystallized from ethanol with a melting point of 71 to 74 '(C, 1 H, ONC12: Calculated 5.8% N. Found: 6, o% N). This a-3 ', 4'-dichlorophenyl-ß-methoxy-ß-methylacrylonitrile was in the the usual way with guanidine (from 4.7 g of the hydrochloride) condensed. The diamino-pyrimidine derivative was separated after heating for 2 hours. Melted after recrystallization from ethanol it at 274 to 275 '.

Calculated for C11H1oN, C12: 2o, 90 /, N. Analysis: 2I, 2 o / 0 N.

Example 34 2,4-Diamino-5- (3 ', 4'-dichlorophenyl) -6-ethylpyrimidine This connection was made as in the previous example. After recrystallization from ethanol water it melted at 229 to 232 '. Example 35 2, 4-Diamino-5- (3 ', 4'-dichlorophenyl) -6-n-propylpyrimidine As above from a-n-butyryl-a-3 ', 4'-dichlorophenylacetonitrile (Melting point: Ioi '). After recrystallization from benzene-ligroin mixtures it melted the connection at 174 to z76 '.

Calculated for C13H14N4C12. 52.5% C, 4.70 / OH, 18.9% N. Found: 52.8 01 / o C, 6.8% H, 18.11 Oi! O N. Example 36 2, 4-diamino- 5- (3 ', 4'-dichlorophenyl) -6-n-butylpyrimidine Prepared as above from anValeryl-a-3', 4'-dichlorophenylacetonitrile. The compound melted at 1 93 to 1.95 '. .

Calculated for C14H16N, C12: 54, I o / o C, 5.20 / OH. Found: 53.8% C, 5.0% H. Example 37 2,4-Diamino-5- (3 ', 4'-dibromophenyl) -6-ethylpyrimidine was used prepared as above from a-propionyl-a-3 ', 4'-dibromophenylacetonitrile. After recrystallization from alcohol the compound melted at 25o to 252 '. Example 38 2,4-Diamino-5- (3'-bromo-4'-chlorophenyl) -6-methylpyrimidine In the manner previously described from α-acetylu-3'-bromo-4'-chlorophenylacetonitrile manufactured; the link melted at 244 to 246 '.

Example 39 2,4-Diamino-5-p-chlorophenyl-6-n-butyl-pyrimidine The condensation of ß-methoxy-ß-n-butyla-p-chlorophenylacrylonitrile with guanidine, as in example 3, gave 2,4-diamino-5-p-chlorophenyl-6-n-butyl-pyrimidine in good yield. After recrystallization from aqueous ethanol, the compound melted at 208 to 21o '. Example 40 2,4-Diamino-5-p-bromophenyl-6-ethyl-pyrimidine The condensation of β-ethyl β-ethoxy-a-p-bromophenylacrylonitrile and guanidine gave 2,4-diaminop-bromophenyl-pyrimidine in good yield. The compound was prepared according to the procedure described in Example 3 cleaned and melted at 213 to 216 '.

Claims (1)

PATEN TANSPRUC13: Process for the preparation of 4-amino-5-arylpyrimidine derivatives of the general formula which are optionally substituted in the 2- and / or 6-position where X denotes a hydrogen atom, an amino, alkyl or aryl group, R denotes a hydrogen atom, an alkyl or aryl group and Ar denotes an aryl group, characterized in that one is a urea derivative of the general formula wherein X has the meaning given above, with a β-alkoxy-a-aryl-acrylonitrile in front of the general formula wherein Ar and R have the meaning given above, ring-closed condensed.