DE1215161B - Process for the preparation of 2-aminopyrimidines substituted in the 5-position - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. α .:

C07d

German class: 12 ρ - 7/01

Number: 1215 161

File number: Sch 29319IV d / 12 ρ

Filing date: March 2, 1961

Opening day: April 28, 1966

The main patent 1145 622 relates to a process for the preparation of 5-arkoxy-2-aminopyrimidines the general formula

NH ₂

wherein R is a lower alkyl group, by reacting 1,1,2-trialkoxyethanes of the general formula

- CH ₂ - CH (OR ') ₂

II

: n —CHO

III

where R ₁ and R _{2 are} alkyl radicals and R _{2 is} also a phenyl radical, completion of the Vilsmeier condensation in the temperature range given above and reaction of the reaction mixture thus obtained with the solution of a guanidine salt and alkali hydroxide or alkali alkanolate in a lower alcohol.

It has now been found that new 2-aminopyrimidines substituted in the 5-position can be obtained general formula I arrives, in which R, however, is an alkyl group which is replaced by one or more Oxygen atoms is interrupted and / or ring-closed, by reaction according to patent 1145 622 using compounds of the general formula II, in which, however, R is an alkyl group, which is interrupted and / or ring-closed by one or more oxygen atoms, and R 'is a means lower alkyl group, instead of the 1,1,2-trialkoxyethanes used as starting materials in the main patent.

example 1

252 g of methoxyethoxyacetaldehyde-dimethoxyethylacetal are slowly mixed with 210 g of phosphorus penta process for the preparation of in 5-position with stirring, ice-cooling and exclusion of moisture
substituted 2-ammopyrimidines

Addendum to the patent: 1145 622

wherein R has the meaning given above and R 'has the meaning of R, with one for the Vilsmeier reaction suitable acidic, halogen-containing condensation agents in such a way that an exchange of a of the two alkoxy groups against halogen, ao and simultaneous or subsequent addition of one Formamides of the general formula

Applicant:

Schering Aktiengesellschaft,

Berlin N 65, Müllerstr. 170/172

Named as inventor:

Dr. Hans Priewe,

Dr. Klaus Gutsche, Berlin

chloride added so that the reaction ^{temperature does not exceed 25 0} C, and then stirred for 30 minutes at room temperature. 225 ml of dimethylformamide are then added dropwise, the reaction temperature being kept at 20 to 25 ° C. by cooling with ice. Thereafter, about 70 minutes to 6O ⁰ C is heated. After cooling, 500 ml of methanol are added dropwise to the reaction mixture while cooling with ice, the reaction temperature not exceeding 20 to 25 ° C. The reaction solution is then added dropwise, likewise with cooling, at a reaction ^{temperature of 20 to 25 °} C. in a suspension of 240 g of powdered caustic soda and 800 ml of methanol and stirred for 30 minutes at room temperature. 200 g of guanidine nitrate and then 70 g of caustic soda are now added to the ^ -dimethylaminooc-methoxyethoxyacrolein now present in the solution in addition to inorganic salts. The methanol is then distilled off with stirring. The distillation residue is dissolved in 1.5 liters of water and extracted several times with chloroform. The combined extracts are concentrated to dryness. After recrystallization from carbon tetrachloride, the distillation residue gives 80 g of 2-amino-5-methoxyethoxypyrimidine; Mp. 80 to 8I ⁰ C.

Example 2

In an analogous manner, 88 g of 2-amino-S-CyClOhCXyIoXyPyHnU-din, mp be 72-73 ⁰ C, obtained from 324 g of 1,1,3-Tricyclohexyloxyäthan..

609 560/474

IO

B e is ρ i e13

430 g of ethoxyethoxyethoxyacetaldehyde di-ethoxyathoxyethyl acetal are analogous to Example 1 with phosphorus pentachloride, dimethylformamide and guanidine nitrate implemented. The crude base obtained from the chloroform extract is diluted in for purification Dissolved hydrochloric acid and extracted several times with ether. The aqueous phase is then washed with sodium hydroxide solution made alkaline and extracted with chloroform. Concentration of the chloroform extracts gives 175 g 2-Armno-5-ethoxyethoxyethoxypyrimidine was obtained as a brown oil.

The base as Benzolsulf onylverbindung (mp. 118-119 ⁰ C), which is represented by the reaction * 5 Base with benzenesulfonyl chloride in pyridine is identified. '

Eg game 4

Analogously to Example 3, from 330 g of tetrahydrofurfuryloxyacetaldehyde - di - tetrahydrofurfurylacetal 130 g of 2-amino-5-tetrahydrodfurfuryloxypyrimidine as brown oil obtained. The benzenesulfonyl compound made to identify the base melts at 213 up to 215 ° C.

Example 5

In a solution of 30 g 1,1,3-Triäthoxyäthoxyäthan (made of Chloracetaldehyddiäthoxyäthylacetal by reaction with the sodium compound of Äthylenglykolmonoäthyläthers;. Kp _u = 17O ⁰ C) in 100 ml of methylene chloride are introduced 27.5 g of phosgene at 30 ° C. Then 23 ml of dimethylformamide are added dropwise to the cooled solution at -5 ° C. The mixture is then stirred for a further 1 hour at moving rather temperature and then heated to 7O ⁰ C. The methylene chloride distills off. Thereafter, the mixture is kept for about _^3/4 hours at 65 ⁰ C. 120 ml of methanol, 20 g of guanidine nitrate and 30 g of sodium hydroxide are added in succession to the reaction mixture, which is then cooled to 20 ^{° C., while cooling.} Finally, the methanol is distilled off with stirring and the distillation residue is exhaustively extracted with perchlorethylene. The combined extracts are evaporated and the residue is recrystallized from carbon tetrachloride. This gives 12 g of 2-amino-5-ethoxyethoxypyrimidine with a melting point of 47 to 49 ° C.

Example 6

(Kp = 150 ₂ ⁰ C made of Chloracetaldehyddiisopropoxyäthylacetal and the sodium compound of Äthylenglykolmonoisopropyläthers.) 13 g of 2-Armno-5-isopropoxyäthoxypyrimidin analogously to Example 5, from 34 g of 1,1,3-Triisopropoxyäthoxyäthan; Fp. About 35 ^° C., b.p. ₀ l ₀₁ = 135 to 140 ^° C.

Claims (1)

Claim: Process for the preparation of substituted in the 5-position 2-aminopyrimidines of the general formula -NH, by implementing connections of the general. my formula - CH (OR ') ₂ with a suitable acid for the Vilsmeier reaction, halogen-containing condensing agent in temperature to 70 ⁰ C and simultaneous or subsequent addition of a formamide of the general "my formula R ₁ . —CHO where R _{1 is} a low molecular weight alkyl group and R _{2 is} a low molecular weight alkyl group or a phenyl group, completion of the Vilsmeier condensation in the above-mentioned temperature range and reaction of the reaction mixture thus obtained with the solution of a guanidine salt and alkali hydroxide or alkali alkanolate in a lower alcohol according to patent 1145 622, characterized that for the preparation of compounds of the general formula I in which R is an alkyl group which is interrupted and / or ring-closed by one or more oxygen atoms, compounds of the general formula II are used as starting materials instead of 1,1,2-trialkoxyethanes , wherein R has the meaning given above and R 'denotes a lower alkyl group. 609 560/474 4.66 © Bundesdruckerei Berlin