DE1149013B - Process for the preparation of 4-oxo-4, 5-dihydro-pyrazolo- [3, 4-d] pyrimidines - Google Patents

Description

The invention relates to a process for the preparation of 4-oxo-4,5-dihydro-pyrazolo [3,4-d] -pyrimidines the general formula

R ₃ -Ns

R4- \ ₇

> ^N

Ri

wherein Ri is a hydrogen atom, an alkyl radical or a phenyl radical, R2 is a hydrogen atom or a lower alkyl radical and R3 is unsubstituted or by hydroxyl groups, halogen atoms or the rest

- N (

R ₅

R ₆

substituted alkyl radical, where R5 and Rö Hydrogen atoms or alkyl groups or together one optionally replaced by an oxygen, sulfur or Represent a nitrogen atom interrupted alkylene radical, and R4 represents an alkyl or aralkyl radical stands, as well as their salts and the quaternary ammonium compounds of the 5-aminoalkyl compounds.

Examples of alkyl radicals are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl (l) -, Pentyl (2), pentyl (3), 2-methylbutyl (3) or hexyl radicals.

A lower alkyl radical R2 is in particular a Methyl radical. R2 preferably stands for a hydrogen atom.

R3 is in particular a lower branched or straight alkyl radical connected at any point, such as a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl (l), pentyl (2), pentyl (3), 2-methylbutyl (3) - or hexyl radical; a hydroxy or haloalkyl radical, such as the hydroxy or chloroethyl or propyl group, or especially a dimethylamino, diethylamino, pyrrolidino, piperidino, Morpholino, piperazino, N-methylpiperazino-ethyl, propyl or butyl radical.

R4 is e.g. B. a lower alkyl radical, such as a methyl, Ethyl, but especially one containing more than 2 carbon atoms, such as propyl, isopropyl, Butyl, isobutyl, pentyl (1), pentyl (2), pentyl (3), 2-methylbutyl (3) or hexyl radical, but especially

4-oxo-4,5-dihydropyrazolo- [3,4-d] pyrimidines

Applicant: CIBA Aktiengesellschaft, Basel (Switzerland)

Representative: Dipl.-Ing. E. Splanemann, patent attorney Hamburg 36, Neuer Wall 10

Claimed priority:

Switzerland from May 11, 1960 and April 4, 1961

(No. 5403 and No. 3929)

Dr. Paul Schmidt, Therwil, Dr. Kurt Eichenberger and Dr. Max Wilhelm, Basel (Switzerland), have been named as inventors

a phenylalkyl, such as 1- or 2-phenylethyl, 1-phenylpropyl or phenylmethyl radical.

The new compounds have valuable pharmacological properties. In particular, they are effective in expanding the coronary artery. The new compounds can thus serve as remedies, especially for circulatory disorders of the heart muscle, but also as intermediate products for the production of such remedies.
The new compounds are superior to known compounds with the same direction of action. For example, l-isopropyl-5- (y-diethylaminopropyl) - 6 - benzyl - 4 - oxo - 4,5 - dihydro - pyrazolo [3,4-d] pyrimidine and l- (sec-butyl) - 5 - (/? - diethylaminoethyl) - 6 - benzyl - 4 - oxo - 4,5 - dihydro - pyrazolo [3,4-d] pyrimidine on the isolated rabbit heart in the experimental arrangement according to Langendorff in a concentration of 10 μg / ml an increase of the coronary flow by 78 or 73%, while the l-isopropyl-4-diethylamino-pyrazolo [3,4-d] pyrimidine obtainable according to the method of German Auslegeschrift 1,056,613 in the same concentration only causes an increase of 60%.

309 597/326

The compounds of the general formula are particularly valuable as coronary-expanding agents

and their salts, in which Ri is a hydrogen atom or, above all, a lower alkyl radical, especially a branched one, such as an isopropyl or sec-butyl radical, R _{3 is} a di-lower alkylamino, pyrrolidino, piperidino, morpholino or piperazino-lower alkyl radical, especially a dimethylamino or diethylaminoethyl or propyl radical and R4 stands for a benzyl radical.

L-sec-butyl-5- (ß-diethylaminoethyl) -6-benzyl-4-oxo-4,5-dihydropyrazolo [3,4-d] pyrimidine is particularly valuable the formula

(C ₂ Hg) ₂ N - CH ₂ - CH ₂ - N
CH ₂

N '

CH

CH ₃ CH ₂ -CH ₃ and its salts.

The new compounds are obtained when either in a manner known per se a) a 4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidine of the general formula

HN

R ₄ -

II

Ri

with a reactive ester of an alcohol of the general formula R ₃ OH or with an aliphatic epoxide or b) a 3-ammo-pyrazole-4-carboxylic acid of the general formula

HOOC-H ₂ N-

R ₂

N /

III

Ri

or their esters or halides with a carboxylic acid of the general formula R ₄ --COOH or their esters, halides, anhydride, amide or imino ethers or the corresponding sulfur derivatives or with the amidine or nitrile in the presence of an amine of the general formula R3 - NH ₂ or c ) a pyrazole derivative of the general formula

R ₃ -HN-OC

H ₂ N

with a carboxylic acid of the general formula R4COOH or its esters, halides, Anhydride, amide or imino ethers or the corresponding sulfur derivatives or with the Amidine or nitrile condensed or d) a 4-0x0-3,4-dihydro-pyrimidine of the general formula

R ₃ -R ₄ -

-R ₂

wherein X stands for a free or etherified mercapto group or a halogen atom, is reacted with a hydrazine of the general formula Ri-NH-NH-R ₇ , wherein R _{7 is} a hydrogen atom or an acyl group, and optionally hydrolyzes the acyl group before or at the same time as the ring closure or

e) a 4-oxo-6-hydrazino-3,4-dihydro-pyrimidine der general formula

R ₃ - R ₄ -

N-NH ₂ I.
Ri

heated with an acid of the general formula R ₂ COOH or a reactive derivative of such an acid or
f) a 4-oxo-pyrazolo [3,4-d] oxazine of the general formula

R ₂ -

Il

y ^c \

O CR ₄

VII

Ri

heated with an amine of the general formula R ₃ - NH ₂

and optionally then in compounds obtained with a hydroxyalkyl or halogen

alkyl group in the 5-position this in one through the rest

Conversion into a reactive ester - with a compound of the general formula

- N

-R ₅
R ₆

HN

R ₅
R ₆

substituted alkyl group converts and / or compounds obtained, which in the 5-position by the rest

- N

R ₅
R ₆

contain substituted alkyl group, quaternized and / or obtained free compounds in their salts or the salts obtained are converted into the free compounds.

As reactive esters are in the procedure a) in particular those strong inorganic or organic acids, e.g. B. of hydrohalic acids, Sulfuric acid or organic sulfonic acids, e.g. B. Arylsulfonic acids, such as toluenesulfonic acids, to call. The reaction is carried out in the usual way, expediently in the presence of basic condensing agents, such as alkali hydroxides, alcoholates, hydrides or amides.

The reaction according to procedure c) can, for. B. be done so that a 3-amino-pyrazole-4-carboxamide, which is substituted on the amide nitrogen atom by the radical R3, with an ester, halide, Imino ether, thioimino ether or nitrile of a carboxylic acid of the general formula R4 - COOH implements.

Procedures b) and c) are preferably carried out at higher temperatures, if appropriate in Presence of diluents and / or condensation agents in the open or closed vessel carried out.

In procedure e), the acid of the general formula R2COOH is preferably in the form their reactive derivatives, such as their anhydrides or optionally orthoesters, are used.

In the reaction according to procedure f), the acid amide is formed as an intermediate. As starting materials Oxazines used are z. B. by dehydration from 4-carboxy-pyrazoles of the general formula

Compounds of basic character obtained form salts with inorganic or organic ones Acids. As salt-forming acids, for example, those that can be used therapeutically come into consideration: hydrohalic acids, Sulfuric acid, phosphoric acid, nitric acid, perchloric acid; aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids, such as formic, acetic, propionic, oxalic,

Amber, glycol, milk, apple, wine, lemon, Ascorbic, hydroxymaleic, dihydroxymaleic, or pyruvic acid; Phenyl acetic, benzoin, p-aminobenzoic, Anthranilic acid; Methanesulphonic, ethanesulphonic, oxyethanesulphonic, ethylene sulphonic acid; Toluenesulfone, Naphthalenesulfonic acids or sulfanilic acid; Methionine, tryptophan, lysine, arginine, or cysteine Glutamic acid. Salts obtained can be converted into the free bases, and free bases can be converted into their salts.

The new pharmacologically valuable compounds, their salts or their mixtures can e.g. B. find use in the form of pharmaceutical preparations.

If the starting materials used in the process according to the invention are new, they can be used according to methods known per se or described here.

The 4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidines of the general formula II used as starting materials can be obtained by reacting 3-amino-4-carbethoxypyrazoles substituted in the 2-position by the radical Ri with nitriles general formula R4CN can be obtained using sodium as a condensing agent.
The invention is described in more detail in the following examples, the notation with the most nuclear double bonds being chosen for the pyrazolo [3,4-dlpyrimidines used as starting materials. The temperatures are given in degrees Celsius.

example 1

COOH

NH - CO - R ₄

z. B. by means of anhydrides, such as acetic anhydride, obtained.

Obtained tertiary amines can be in the usual way, for. B. quaternize with reactive esters of alcohols such as alkanols or phenylalkanols. Hydroxyalkyl or haloalkyl radicals in the 5-position of the compounds obtained can be converted into amino or ammoniumalkyl radicals in a manner known per se. This conversion takes place, for example, by reacting a hydroxyalkyl or haloalkyl compound - in the case of the hydroxyalkyl compound after a solution of 5.4 g of 1-isopropyl-4-hydroxy-6-benzyl-pyrazolo [3,4-d] pyrimidine in 30 cm ³ 1 N sodium hydroxide solution is ^{mixed with 1.95 cm 3 of} dimethyl sulfate,

so and it is stirred for 1 hour at room temperature. The alkaline solution is then extracted with ether and the ether residue is crystallized from petroleum ether. 1-Isopropyl-S-methyl-o-benzyl ^ -oxo ^ S-dihydro-pyrazolol3,4-d] pyrimidine is obtained in colorless crystals with a melting point of 96 to 97 ° (Yield: 4.2 g).

The starting material is obtained as follows:
2.3 g of sodium are finely ground in 50 cm ^{3 of} benzyl cyanide and 9.9 g of 2-isopropyl-3-amino-4-carbethoxy-pyrazole are added. The mixture is then heated to 110 ° to 120 ° for 4 hours with stirring, treated with 100 cm ^{3 of} alcohol after cooling and evaporated to dryness in a vacuum. The residue is taken up in 150 cm ^{3 of} 2 η sodium hydroxide solution, the alkaline solution is extracted by shaking with chloroform to separate off undissolved material and then adjusted to pH 5 to 6 with 6N hydrochloric acid, a solid product precipitating out. The latter becomes a little

Recrystallized alcohol. 1-Isopropyl-4-hydroxy-6-benzyl-pyrazolo [3,4-d] pyrimidine is obtained in this way the formula

OH

CH ₂

in colorless coasts with a melting point of 165 to 166 °.

Example 2

To 14.1 g l-sec-butyl ^ -hydroxy-ö-benzyl-pyrazolo [3,4-d] pyrimidine in 60 cm ³ of absolute ethanol, a solution of 1.15 g of sodium are added in 40 cm ³ of absolute alcohol, and after the addition of 7.5 g of diethylamino-ethyl chloride it is refluxed for 4 hours. After cooling, the precipitated crystals are filtered off with suction, the filtrate is evaporated, the residue is treated with 50 cm ^{3 of} 1 η-hydrochloric acid and a little undissolved material is filtered off. The filtrate is adjusted to pH 10 with 2 η sodium hydroxide solution and extracted with ether. The oil obtained from the ether residue is dissolved in 30 cm ^{3 of} absolute alcohol and ^{mixed with 28.4 cm 3 of} 49 normal alcoholic hydrochloric acid. The residue obtained from the evaporated reaction solution is l-sec-butyl-5 - (/ ^ diethylaminoethyl-6-benzyldes hydrochloride with a melting point of 147 ° to 148 ° (yield: 15.3 g).

The 1-sec-butyl-4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidine used as starting material in the form of 4-hydroxy-6-benzyl-pyrazolo [3,4-d] pyrimidine can be obtained as follows:

13.8 g of sodium are added in small pieces to 200 cm ^{3 of} benzyl cyanide, followed by 63.3 g of 2-sec-butyl-3-amino-4-carbethoxypyrazole. The mixture is heated to 110 to 120 ° in about 30 minutes and then stirred at this temperature for a further 5 hours. After cooling, absolute alcohol is added and the mixture is concentrated in vacuo. Dilute sodium hydroxide solution is added to the residue and the mixture is extracted with chloroform. The aqueous alkaline solution is treated with activated charcoal and filtered. The clear filtrate is adjusted to pH 6 with 5η hydrochloric acid, whereupon the 1-sec-butyl-4-hydroxy-6-benzyl-pyrazolo [3,4-d] pyrimidine of the formula

Example 3

In a sodium ethylate solution, prepared from 1.2 g of sodium and 300 cm ^{3 of} anhydrous alcohol, 13.4 g of 1-isopropyl- ^ hydroxy-o-benzylpyrazolo [3,4-djpyrimidine are added. To form the sodium salt, the mixture is stirred at room temperature for 1 hour. 5.5 g of I-dimethylamino-ethyl chloride are added, the mixture is heated to boiling for 4 hours, then evaporated to dryness in vacuo, the residue is dissolved in 100 cm ^{3 of} 1 η-hydrochloric acid, and the pn value is adjusted to 10 with sodium hydroxide solution and absorbs the precipitated oil in ether. The ether residue is recrystallized from petroleum ether. 1-Isopropyl-5 - (/? - dimethylaminoethyi) -6-benzyl-4-oxo-4,5-di-hydro-pyrazolo [3,4-d] pyrimidine is obtained in colorless crystals with a melting point of 115 ° to 117 ° obtained (yield: 10.2 g). The hydrochloride melts from 229 to 231 °.

OH

CH ₂

55

60

separates, which melts after recrystallization from alcohol at 154 to 155 °.

Example 4

13.4 g of l-isopropyl - ^ - hydroxy-ö-benzylpyrazolo [3,4-d] pyrimidine are introduced into a sodium ethylate solution prepared from 1.2 g of sodium and 300 cm ^{3 of anhydrous alcohol.} To form the sodium salt, the mixture is stirred at room temperature for 1 hour. 7 g / J diethylamino-ethyl chloride are added, the mixture is heated to boiling for 4 hours, then evaporated to dryness in vacuo, the residue is dissolved in 100 cm ^{3 of} 1 η-hydrochloric acid, adjusted to 10 with sodium hydroxide solution and taken precipitated oil in ether. The ether residue is mixed with alcoholic hydrochloric acid. The latter is evaporated and the residue is recrystallized from ethyl acetate. The hydrochloride of 1-isopropyl-5 - {ß -diethylaminoethyl) -6-benzyl-4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidine is thus obtained in colorless crystals; M.p. 202 to 203 ° (yield: Π g)

Example 5

13.4 g of 1-isopropyM-hydroxy-o-benzylpyrazolo [3,4-d] pyrimidine are introduced into a sodium ethylate solution prepared from 1.2 g of sodium and 300 cm ^{3 of anhydrous alcohol.} To form the sodium salt, the mixture is stirred at room temperature for 1 hour. 8 g of γ-diethylaminopropyl chloride are then added, the mixture is heated to boiling for 4 hours, then evaporated to dryness in vacuo, the residue is dissolved in 100 cm ^{3 of} 1N hydrochloric acid, adjusted to pH 10 with sodium hydroxide solution and taken the precipitated oil in ether. The ether residue is recrystallized from petroleum ether. l-isopropyl-5- (y-diäthylaminopropyl) -6-benzyl-4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidine is obtained as ¹ in colorless crystals of melting point 70 ° to 71 ° (yield : 10 g). The hydrochloride melts at 173 to 175 °.

Example 6

1.2 g of sodium in 25 cm ^{3 of} ethanol are added to 12 g of l-methyl-hydroxy-o-benzyl-pyrazolo- [3,4-d] pyrimidine in 75 cm ^{3 of alcohol.} It is refluxed for 1 hour and then 6 g /? - Di-

ethylamino-ethyl chloride, followed by a further 3 hours is heated to boiling. The precipitated sodium chloride is filtered off and the filtrate is evaporated one and the residue is recrystallized from cyclohexane. 1-Methyl-5 - (/? - diethylaminoethyl) -6-benzyl-4-oxo-4,5-dihydro-pyrazolo- [3,4-d] pyrimidine is obtained in crystals of melting point 83 to 85 "(yield: 6.2 g). The hydrochloride melts at 219 °.

The 1-methyl-4-hydroxy-6-benzyl-pyrazolo [3,4-d] pyrimidine used as starting material is obtained as follows:

2.3 g of sodium are added in small pieces to a solution of 8.5 g of 2-methyl-3-amino-4-carbethoxy-pyrazole in 50 cm ^{3 of} benzyl cyanide and then heated to 110 ° to 120 ° with stirring. After 4 hours the reaction mixture is cooled and 100 cm ^{3 of} ethanol are added. The solution is evaporated to dryness in vacuo. ^{150 cm 3 of} 2 η sodium hydroxide solution are added to the residue and the excess benzyl cyanide is extracted with chloroform. The aqueous phase is adjusted to a pn value of 5 to 6 by adding 5N hydrochloric acid, a solid precipitate separating out, which is filtered off and recrystallized several times from ethanol. The 1-methyl-4-hydroxy-6-benzyl-pyrazolo [3,4-d] -pyrimidine of the formula is obtained

crystallized. The l-phenyl-4-hydroxy-6-benzyl-pyrazolo [3,4-d] pyrimidine is obtained in this way the formula

OH

CH ₂

in colorless crystals with a melting point of 264 to 265 °.

Example 8

CH ₂

in crystals with a melting point of -236 to 237 °.
Example 7

A solution of 800 mg of sodium in 10 cm ^{3 of} ethanol is added to a suspension of 10 g of 1-phenyl-6-benzyl-4-hydroxypyrazolo [3,4-d] pyrimidine in 100 cm ^{3 of} ethanol and refluxed for 30 minutes cooked. Then add 5.g /? - diethylamino-ethyl chloride in 10 cm ^{3 of} alcohol and cook for a further 3 hours. The precipitated sodium chloride is filtered off and the filtrate is evaporated to dryness in vacuo. The solid residue is recrystallized from cyclohexane-petroleum ether and l-phenyl-5 - (/? - diethylaminoethyl) - 6 - benzyl - 4-oxo - 4,5 - dihydro - pyrazolo- [3,4-d] pyrimidine in crystals with a melting point of 103 to 105 ° (yield: 7.5 g). The hydrochloride melts at 225 °.

The 1-phenyl-6-benzyl-4-hydroxy-pyrazolo used as the starting material [3,4-d] pyrimidine is obtained as follows:

2.3 g of sodium are added in small pieces to a mixture of 12 g of 2-phenyl-3-amino-4-carbethoxy-pyrazole and 50 g of benzyl cyanide and the mixture is heated to 140 ° for 4 hours with stirring. After cooling, 100 cm ^{3 of} alcohol are added to the reaction mixture and the pH is adjusted to 5 to 6 with 2η hydrochloric acid. A precipitate separates out, which is prepared from chloroform-petroleum ether in a sodium ethylate solution

1.2 g of sodium and 150 cm ^{3 of} anhydrous ethanol, 9.1 g of 1-isopropyM-hydroxy-o-methylpyrazolo [3,4-d] pyrimidine are added. For education

of the sodium salt is stirred for 1 hour at room temperature. 7 g of S-diethylaminoethyl chloride are added, the mixture is heated to boiling for 4 hours, then evaporated to dryness in vacuo, the residue is dissolved in 100 cm ^{3 of} 1 η-hydrochloric acid, adjusted to pH 10 with sodium hydroxide solution and the precipitated product is taken Oil in ether. The ether residue is mixed with alcoholic hydrochloric acid. The latter is evaporated and the residue is recrystallized from ethyl acetate. The hydrochloride of 1 - isopropyl -5- {ß- diethylaminoethyl) - 6 - methyl-4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidine with a melting point of 166 ° to 168 ° is obtained (yield: 7 g).

The 1-isopropyl-4-hydroxy-6-methyl-pyrazolo [3,4-d] pyrimidine used as the starting material is obtained as follows:

To a solution of 9.9 g of 2-isopropyl-3-amino-4-carbethoxy-pyrazole in 50 cm ^{3 of} acetonitrile is added

2.3 g sodium with ice cooling. The temperature must not rise above 30 ° during the reaction.

As soon as the exothermic reaction has ended, the mixture is heated to 90 to 95 ° for 4 hours. The reaction mixture is then cooled and 100 cm ^{3 of} ethanol are added. It is evaporated to dryness in vacuo, 150 cm ^{3 of} 2 η sodium hydroxide solution are added to the residue and the excess acetonitrile is extracted with chloroform. The aqueous phase is adjusted to a pn value of 3 to 4 by adding 5η hydrochloric acid, a solid precipitate separating out after prolonged standing, which is filtered off and recrystallized from ethanol. The l-isopropyl ^ hydroxy-o-methyl-pyrazolo [3,4-d] pyrimidine of the formula is obtained

CH (CHg) ₂
in white crystals with a melting point of 195 to 196 °.

309 597/326

Example 9

6.3 g of dimethyl sulfate are added to a solution of 11 g of 1,6-diisopropyl-4-hydroxypyrazolo [3,4-d] pyrimidine in 75 cm ^{3 of} 2N sodium hydroxide solution, and the mixture is stirred at room temperature for 2 hours and left to stand overnight . The precipitate is then filtered off with suction and crystallized from petroleum ether. 1,6-Diisopropyl-5-methyl-4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidine is obtained in this way in colorless crystals with a melting point of 75 ° to 77 ° (yield: 9 g).

The 1,6-diisopro used as starting material. pyl-4-hydroxy-pyrazolo [3,4-d] pyrimidine is like is obtained as follows:

39.6 g of 2-isopropyl-3-amino-4-carbethoxy-pyrazole and 9.2 g of finely comminuted sodium are introduced into 160 cm ^{3 of isobutyronitrile.} The mixture is heated to 110 ° over the course of one hour and this temperature is maintained for 4 hours with stirring. After cooling, 15 cm ^{3 of} ethanol are added, the mixture is evaporated to dryness in vacuo, the residue is taken up in 100 cm ^{3 of} 2 η sodium hydroxide solution and the alkaline solution is extracted with chloroform. The aqueous phase is adjusted to pH 5 to 6 by adding 5η hydrochloric acid, a solid product precipitating out. The latter is recrystallized several times from ethanol. 1-Isopropyl ^ -hydroxy-o-isopropylpyrazolo [3,4-d] pyrimidine of the formula

OH

methyl 5 - (/ 3-diethylaminoethyl) -4-oxo-4,5-dihydropyrazolo [3,4-d] pyrimidine is obtained in colorless crystals with a melting point of 124 to 125 ° (yield: 3.8 g).

The 1-isopropyl-4 - hydroxy - 6 - diphenylmethyl - pyrazolo [3,4 - d] pyrimidine used as starting material is obtained as follows:
-, 20 g of diphenylacetonitrile and 19.7 g of 2-isopropyl-3-amino-4-carbethoxy-pyrazole are heated to 70 ° and mixed with 2.3 g of sodium in small pieces. The mixture is then heated for 4 hours at 110 ° to 120 °, allowed to cool, the excess sodium is destroyed with ethanol and evaporated to dryness in vacuo. 300 cm ^{3 of} water are added to the residue, and the pH is adjusted to 3 with 2N hydrochloric acid, whereupon a solid precipitate separates out. The latter is sucked off, boiled with a lot of petroleum ether to separate any starting material that is still present, and the portion not dissolved in petroleum ether is recrystallized from ethanol. 1-Isopropyl-4-hydroxy-6-diphenylmethyl-pyrazolo [3,4-d] pyrimidine of the formula

OH

(CHg) ₂ CH

CH (CHs) ₂

is obtained in this way in white crystals with a melting point of 175 to 177 °.

Example 10

10 g of 1,6-diisopropyl-4-hydroxypyrazolo [3,4-d] pyrimidine are introduced into a sodium ethylate solution prepared from 1.05 g of sodium and 150 cm ^{3 of ethanol.} To form the sodium salt, the mixture is stirred at room temperature for 1 hour. 6.5 g of (S-diethylamino-ethyl chloride) are added, the mixture is heated to boiling for 4 hours, then evaporated to dryness in vacuo, the residue is dissolved in 100 cm ^{3 of} 1N hydrochloric acid, adjusted to a pn value of 10 with sodium hydroxide solution the precipitated oil is taken up in ether. The ether residue is distilled. 1,6-Diisopropyl-5 - (^ - diethylaminoethyl) -4-oxo-4,5-dihydro-pyrazolo- [3,4-d] pyrimidine goes at 138 to 140 ° at a pressure of 0.05 mm Hg above (yield: 9 g).

Example 11

5.2 g of 1-isopropyl-4-hydroxy-6-diphenylmethyl-pyrazolo- [3,4-d] pyrimidine are added to a sodium ethylate solution prepared from 0.35 g of sodium and 150 cm ^{3 of ethanol.} To form the sodium salt, the mixture is stirred at room temperature for 1 hour. 2.1 g / i-diethylaminoethyl chloride are added, the mixture is heated to boiling for 4 hours, evaporated to dryness in vacuo and the residue is crystallized from petroleum ether. 1-isopropyl-6-diphenyl-CH (CHa) ₂

is thus obtained in white crystals with a melting point of 226 to 227 °.

Claims (1)

PATENT CLAIM: Process for the preparation of 4-oxo-4,5-dihydro - Pyrazolo [3,4 - d] pyrimidines of the general formula where Ri is a hydrogen atom, an alkyl group or a phenyl group, R _{2 is} a hydrogen atom or a lower alkyl group and R3 is an unsubstituted or hydroxyl group, halogen group or the group - Ν R ₅ R ₆ Substituted alkyl radical, where R5 and Re represent hydrogen atoms or alkyl groups or together represent an alkylene radical optionally interrupted by an oxygen, sulfur or nitrogen atom, and R4 represents an alkyl or aralkyl radical, and of their salts and the quaternary ammonium compounds of the 5-aminoalkyl compounds , characterized in that either in a known manner a) a 4-oxo-4,5-dihydro-pyrazolo [3,4-d] pyrimidine of the general formula
O HN R ₂ R ₄ - I.
Ri R ₃ -HN-OC
H ₂ N R ₂ 10 with a reactive ester of an alcohol of the general formula R3OH or with an aliphatic epoxide or b) an S-amino-pyrazoM-carboxylic acid of the general formula or their esters of the halides with a carboxylic acid of the general formula R ₄ - COOH or their esters, halides, anhydride, amide or amino ethers or the corresponding sulfur derivatives or with the amidine or nitrile in the presence of an amine of the general formula R3 - NH2 or
c) a pyrazole derivative of the general formula 35 40 with a carboxylic acid of the general formula R4 - COOH or its esters, Halides, anhydride, amide or imino ethers or the corresponding sulfur derivatives or condensed with the amidine or nitrile or d) a 4-oxo-3,4-dihydro-pyrimidine of the general formula R ₃ -N —R ₂ 55 wherein X stands for a free or etherified mercapto group or a halogen atom is, with a hydrazine of the general formula Ri-NH-NH-R ₇ , in which R _{7 is} a hydrogen atom or an acyl group, is reacted and optionally hydrolyzed or removed from the acyl group before or at the same time as the ring closure
e) a 4-oxo-6-hydrazino-3,4-dihydro-pyrimidine of the general formula heated with an acid of the general formula R2COOH or a reactive derivative of such an acid or
f) a 4-oxo-pyrazolo [3,4-d] oxazine of the general formula R ₂ ■ Ν * Ri heated with an amine of the general formula R ₃ - NH2 and optionally then in compounds obtained with a hydroxyalkyl or Haloalkyl group in the 5-position this in one through the remainder - N R ₅
R ₆ substituted alkyl group converts and / or compounds obtained which are in the 5-position through the rest - N R ₅
R ₆ contain substituted alkyl group, quaternized and / or obtained free compounds in their Salts or salts obtained converted into the free compounds. Considered publications:
German interpretation document No. 1 056 613. © 309 597ßZ6 5.63