DE1695893C - Process for the preparation of 4 amino 5 acylamidomethyl pynmidines - Google Patents

Description

It has been found that one can use the J-Aminti-S-acylumidmeihylpyrimidines of the general formula which are valuable _{for the production of vitamin H 1 and its derivatives}

N = C-NH,

I I

RC C-CH ₁ NHCOR

II Il

N-CH

in which R is a methyl, ethyl or phenyl group, easily and in high yield as a result can produce, as Ii one, possibly in sword an inert solvent, an amidine of the general formula

NH

Il

R -C- NH,

at cooling to reflux temperature with 1,2,3-Trichlur-2-cyanpmpan converts and hydrolyzes the reaction product. This reaction is surprising. It is assume that it follows the following pattern:

N = C-N- = C-R

RC C-CH ₁ -NH

Cl-CH, -C-CH, CI + 4R-C-NH

N- = C-N = C-R

♦ R-C C-CH, NHCOR

RC C-CH ₂ -NH

NH

+ NH ₄ CI + 2 R-CNH ₂ Ci

l, 2.3-trichloro-2-cyanopropane (boiling point 79 to 80 C at 10 Torr, melting point 23 C) is a new compound. It can be achieved by implementing chlorine gas with 3Chlor-2-cyanpropane under irradiation with light whose wavelength is beyond the visible range does not go beyond being made.

The reaction with the compound is preferably carried out at room temperature, but can may be accelerated by heating. A solvent is not always required for the reaction required, but one which does not inhibit the reaction, e.g. B. Methanol or ethanol, ketones such as acetone or methyl ethyl ketone or hydrocarbons such as benzene, Toluene and xylene.

The free amidine required for the reaction can advantageously be obtained from its salts with acids, e.g. B. hydrochloric acid and sulfuric acid, can be obtained by reaction with the theoretical amount of alcoholate.

Then after reaction with 1,2,3-trichloro-2-cyanopropane The reaction mixture obtained is then immediately or after separation or purification so subjected to hydrolysis.

Hydrolysis is known per se (« Methods carried out e.g. B. by the action of water on the reaction mixture during this is heated.

In the following examples, parts by weight relate to parts of volume like grams to milliliters.

Example I.

20.7 parts by weight of metallic sodium are mixed with 200 parts by volume of methanol, a meihanol solution containing sodium methylene being obtained. 94.6 parts by weight of acetamidine hydrochloride are added to the methanol solution. The mixture is stirred vigorously at room temperature for 1 hour, whereupon the sodium chloride is filtered off. 17.2 parts by weight of 1,2,3-trichloro-2 ”cyanoorooane are coarse to the pillrate, whereupon JOO parts by volume of methanol are removed. The mixture is then refluxed for 10 hours. The methanol is distilled off. After adding 60 parts of downy water to the residue, the mixture is heated to 90 ° C. for 1 hour, during which the hydrolysis takes place.

The precipitate formed by cooling is recrystallized from water, 11.5 parts by weight 2-methyl ^ -amino-S-acetamidomethylpyrimidine was obtained which contain 1/2 mole of water of crystallization and melt at 203-204 ° C.

Example 2

11.5 parts by weight of metallic sodium will be mixed with 150 Raumtcilen methanol, whereby a methanol solution is obtained, the sodium methylate contains. 52.0 parts by weight of acetamidine hydrochloride are added to the methanol solution. The mixture is stirred vigorously at room temperature for 1 hour and then filtered to remove the sodium chloride. 17.2 parts by weight of 1,2,3-trichloro-2-cyynpropane are added to the filtrate given, whereupon 70 parts by volume of methanol are removed. The mixture is then applied to the In the manner described in Example I worked up, with 7.6 parts by weight of 2-methyl ^ -amino-S-acetamidomethylpyrimidine obtained, the ½ mol of water of crystallization contain.

Example 3

To a solution of 29 parts by weight of acetamidine in 50 parts by weight of benzene is a solution of

8.6 parts by weight l, 2,3-Trk: chloro-2-cyanpropun in 50 parts by volume of benzene given below 10 "C, whereupon the mixture is refluxed for 8 hours. By removing the solvent from the mixture under A residue is obtained under reduced pressure, to which 20 parts by volume of water are added. The Mixture is hydrolyzed by heating on WC for 1 hour. The mixture obtained is on the worked up in the manner described in Example I, wherein

5.7 Parts by weight ZMhl ^ iSid

695

IO

IS

Hiethylpyrimidin containing ¹ /, muI crystal water are obtained.

Example 4

For N, 6 parts by weight of l ^ -Trichlor ^ -cyanpropane 20 parts by weight of acetamidine are added dropwise with cooling, followed by 20 parts by volume of water can be added. The mixture is heated to 90 ° C. for 1 hour. After the reaction, the water is removed from the The reaction mixture is distilled off and the residue is extracted with chloroform. Analysis of the chloroform layer shows by paper chromatography that 2.1 parts by weight of 2-methyl-4-amino-5-acetamidomethylpyrimidine have been formed.

Example 5

5.7 parts by weight of metallic sodium are mixed with 100 parts by volume of methanol, with a methanol solution containing sodium methylate. 27.2 parts by weight of propioamidine hydrochloride are added to the methanol solution given. The mixture is agitated for 30 minutes at room temperature.

8.6 parts by weight of 1,2,3-trichloro-2-cyanopropane are added to the mixture obtained. The mixture is refluxed for 8 hours, after which the sodium chloride is removed. The filtrate is under concentrated to dryness under reduced pressure. The residue is extracted with acetone and the Extract concentrated to dryness. After adding 10 parts of water, the aqueous solution becomes Heated for 1 hour to 90 ° C. The mixture is distilled to remove the water and then through Purified chromatography on aluminum oxide, 5.1 parts by weight of 2-ethyl-4-a.nino-5-propionylamidomethylpyrimidine from melting point 187 to 189 ° C can be obtained.

Example 6

A melhanol solution containing sodium methylate is prepared by mixing 5.7 parts by weight of metallic in nitrium with HM) parts by volume of methanol. After adding 4.5 parts by weight of benzamidine to the methanol solution, the mixture is agitated for 30 minutes at room temperature. 8.6 parts by weight of 1,2,3-trichloro-2-cyanopropane are added to the resulting mixture. The mixture is refluxed for 8 hours The sodium chloride is then removed. The filtrate is concentrated to dryness. The dry substance is washed with water and then dissolved in a mixture of 40 parts sodium hydroxide (10%) and 120 parts ethanol, whereupon the mixture is heated on a water bath for 3 hours. the insolubles are ahfiltriert from Reaktiopsgcmisch. the filtrate is cooled to give 2.1 parts by weight of 2-phenyl-4-amino-5-r, enzoylamidomethylpyrimidin of melting point 233-235 C are obtained.

Claims (1)

Claim: Process for the preparation of 4-amino-5-acylamidomethylpyrimidines the general formula N = C-NH ₂
RC C-CH ₂ NHCOR I! Il N-CH in which R is a methyl, ethyl or phenyl group, characterized in that that, optionally in the presence of an inert solvent, an amidine of the general formula NH Il R - C - NH ₂ at cool to reflux temperature with 1,2,3-trichior-2-cyanopropane converts and hydrolyzes the reaction product.