SK53794A3 - Method of preparation of 3,7-dihydro-3-alkyl-1h-purine-2,6-diones - Google Patents

Abstract

This patent describes a procedure closed to the preparation of 3,7-dihydro-3-alkyl-1H-purine-2,6-diones with a formula (I), where R is a hydrogen atom, methyl, ethyl group closed to 1-alkyl-5-nitroso-6-amino-2,4/1H,3H/-pyrimidione with a formula (II), where R is methyl, ethyl, and this production procedure is based on that principle, that the compound with a formula (II) is suspended in water and after that a hydrogenation, at the temperature of 20 up to 100 Celsius degrees and hydrogen pressure of 0,1 up to 3 MPa, is provided, while the catalysts based on Pd or Ni on the active carbon is present, however 1 up to 2 equivalents of formic acid are added, after the equimolar hydrogen quantity is consumed, and this acid is acting 1 up to 8 hours, and after that the mixture is alkalinised with the use of 1 up to 3 equivalents of alkali hydroxide, at the temperature of 30 up to 100 Celsius degrees, for 0,5 up to 5 hours and the substance with a formula (I) is created, after the pH value has been corrected.

Description

A process for the preparation of 3,7-dihydro-3-alkyl-1H-purine-2,6-dione

Qh.La5..ť "t.admi.kx

The invention relates to a process for the production of chemical substances, in particular xanthine derivatives.

ilQiejs ^ l.4i Ä.tiay .... "." ± eLC.bai.Ly.

To date, compounds of formula I have been prepared from the starting material of formula II by reduction. zinc powder in sulfuric acid / Merck: DRP 161493, T.Ukai:

J. Pharm. Soc.Japan 74,674,677 (1954)], by reduction of iron powder or sawdust in an aqueous solution of HCl or MH + Cl (EIAbramova: Khim.Farm.Zh. 9, (1), 32, (1975)) . After reduction, the unreacted reducing agent must be removed from the reaction mixture and then treated with formic acid and cyclized to give the desired compound of formula I. The procedure of M. F. Olonowski et al.

Bul1.Soc.chim. 1946, 80 uses NaaSaOa to reduce the aqueous environment, where further processing releases large amounts of SO2. According to Z. Suzuki et al. Japanese Patent No. 49-81393, xanthine derivatives are prepared by reduction of cyanacetic acid derivatives inormamide at high temperature.

The invention relates to a process for the preparation of 3,7-dihydro-3-alkyl 1-1H-purine-2,6-dione of the formula

H-N

(1) methyl, ethyl (11) (1H). 3 H / - p y r i m. d n n i n v z a a a a a: a

Wherein R is H, methyl, ethyl, n-propyl I, by suspending the compound of formula II in water, 1 to 5% by weight is added thereto. hydrogenation catalyst, based on the weight of compound II, containing 0.5 to 5 Z Pd or 1 to 10 Z Ni in the form of a boride. The mixture is mixed with vigorous stirring at 20 to 100 ° C and a hydrogen pressure of 0.1 to 3 MF. and wherein after use ekvimo1árneho amount of hydrogen was added to the mixture 1 to 2 equivalents of formic acid which is treated at 20 to 100 ⁰ C for 1 S hours., then the mixture was made basic by the addition of 1 to 3 equivalents of alkali metal hydroxide · , preferably NaOH ·, which is left to react at 30 to 100 ° C for 0.5 to 5 hours and after adjusting the pH to 5, the salt of the compound of formula I is obtained by filtration.

The above process yields compounds of formula I in high yield and high purity.

An advantage of the invention is that the hydrogenation is carried out in a neutral environment at low temperature and the product of the formula I obtained is a symbol. o u č d. s t o t o u ,,

FxJJdLacLy ........ E £ syad.ecjLa

Example 1

2, S 1 h i d r o g e n o n c h a lavau lasers

1-methyl ... 5-n d. trose-6-aminouracyl, 100 ml distilled water and 5 g

0.6% Pd on activated carbon. The reactor is sealed and purged 2 times with nitrogen and 2 times with hydrogen. After heating to 60 ° C, it is hydrogenated under vigorous stirring at 50 psi. After 2.5 hours, an equimolar amount of hydrogen was consumed. After cooling to 30 ° C, the hydrogenation mixture is removed, 30 ml of 35% formic acid are added thereto, and the mixture is heated to 100 ° C, where the mixture is maintained for 3 hours. 40 g of sodium hydroxide in 50 ml of distilled water, heated to 85 ° C, with stirring for 1 hour. The catalyst is then filtered off from the reaction mixture, acidified to pH 5 with acetic acid, and the precipitated product is filtered off, washed with water and dried, yielding 73 g of 3-methyl-aniline.

F 'is 1 and d 2

Identical to Example 1, except that 10 g of NiaB as catalyst is used for hydrogenation. 64 g of 3-methylxanthine are obtained, which is a yield. 77 From theory,

Example 3

Identical to Example 1, except that the hydrogenation was carried out at 80 ° C. 66.4 g of 3-methyl-1-methanone were obtained, yielding a yield of 80 ° C. theory.

The compounds obtained are used in the further synthesis of pharmaceutically active substances, for example theobromine. The invention is applicable in the chemical and pharmaceutical industries.

Claims (2)

PATENT N O R O K Y 1) A process for the preparation of a 3,7-dihydric formula Ji. 0 'N- N' ' I À 3-Alkyl-1H-purine-2,6-dione (1) where is H, methyl, ethyl, n-propyl 1 - a 1 k y 1 - 5 - n i. t r o z - 6 - and min o - 2 ·, 4 (1H, 3 H) - p yr, i. m a. d ť n d .i. ó n for the formula H - Ν 'V - NO / 11 / 0 NH_ I 2 where R 1 is H ·, methyl 1, e t? 1, n-propy 1, characterized by. A process according to claim 1, wherein the compound of formula I is prepared from the starting compound of formula II by a one-step process consisting of catalytic hydrogenation in a neutral medium followed by treatment with formic acid and hydroxide and a alkaline metal. (2) The process of claim 1 wherein 0.5 to 5 / F'd on activated carbon or 1 to 10% nickel boride on activated carbon is used as the hydrogenation catalyst. The process according to point h y g e cation is carried out The process according to point hydrogenation is carried out 1, characterized in that at a temperature of 20 to 100 ° C, 1 is characterized. 3. The method according to claim 1, characterized in that it is catalytic Se catalytic 2. The process of claim 1, wherein the catalytic hydrogenation is treated with 1 to formic acid at a temperature of? 20 to 100 ° C per mixture after equivalents