SU910621A1

SU910621A1 - Process for producing 4,5,6-triamino pyrimidine

Info

Publication number: SU910621A1
Application number: SU792847534A
Authority: SU
Inventors: Майя Борисовна Колесова; Хьена Лазаревна Александр; Михаил Вадимович Корсаков; Виктор Владимирович Белогородский; Борис Александрович Ивин; Феликс Борисович Найдис
Original assignee: Ленинградский химико-фармацевтический институт; Научно-Исследовательский Институт Онкологии Им.Н.Н.Петрова
Priority date: 1979-12-04
Filing date: 1979-12-04
Publication date: 1982-03-07

Description

Изобретение относитс к тонкому органическому синтезу, а именно к способу получени 4,5/6-тpиaминoпиpшIИДИнa .This invention relates to fine organic synthesis, in particular to a method for producing 4,5 / 6-tri-aminopyryl IIDIN.

4,5,6-Триаминопиримидин может найти применение как промежуточный продукт синтеза аденина и новых лекарственных средств, таких, как этаден и мерадин.4,5,6-Triaminopyrimidine can be used as an intermediate product for the synthesis of adenine and new drugs, such as etaden and meradin.

Известен способ получени 4,5,6триаминопиримидина восстановлением 4,6-диамино-5-фенилазопиримидина водородом на никеле Рене при нагревании 1 .A known method for producing 4,5,6triaminopyrimidine is by reducing 4,6-diamino-5-phenylazopyrimidine with hydrogen on Rene nickel by heating 1.

Недостатками этого метода вл ютс применение пожаро- и взрывоопасных веществ, таких, как скелетный катализатор и водород, сложность и многостадийность процесса.The disadvantages of this method are the use of flammable and explosive substances, such as skeletal catalyst and hydrogen, the complexity and multistage of the process.

Наиболее близким к предлагаемому способу вл етс способ получени 4,5,6-триаминопиримидина восстановлением и десульфированием 2-тио-4,б-диамино-5-нитрозопиримидинав присутствии скелетного катализатора - никел Рене при нагревании вначале , до , затем при 80 - 120°С. Процесс протекает в течение 2 - .4 ч 2,The closest to the proposed method is the method of obtaining 4,5,6-triaminopyrimidine by reducing and desulfurizing 2-thio-4, b-diamino-5-nitrosopyrimidine in the presence of a skeletal catalyst, Rene nickel, heated first, before, then at 80-120 ° WITH. The process takes place within 2 - .4 h 2,

Недостатками этого способа вл ютс необходимость специального приготовлени огнеопасного никел Рене , расход которого составл ет 5 кг на 1 кг исходного продукта, взрывоопасность процесса при работе с водородом под давлением, необходимость соблюдени мер безопасности при хранении катализатора -и сложность его приготовлени , а также двухстадийность процесса, требующе .10 го изменени условий его проведени .The disadvantages of this method are the need for special preparation of flammable Rene nickel, the consumption of which is 5 kg per 1 kg of the initial product, the explosion hazard of the process when working with hydrogen under pressure, the need to observe safety measures when storing the catalyst and the complexity of its preparation, as well as the two-stage process requiring a .10 change in its conditions.

Целью изобретени вл етс упрощение технологии процесса.The aim of the invention is to simplify the process technology.

Поставленна цель достигаетс The goal is achieved

15 тем, что при осуществлении способа получени 4,5,6-триаминопиримидина восстановлением и десульфированием 2-ТИО-4,6-диамино-5-нитрозопиримидина при нагревании в присутствии ка20 тализатора в качестве последнего используют сплав никел с алюминием, содержащий 45 - 53 вес. % никел и 47 - 55 вес.% алюмини , и процесс ведут в одну стадию в присутствии 15 by the fact that, when carrying out the method for producing 4,5,6-triaminopyrimidine by reducing and desulfurizing 2-TIO-4,6-diamino-5-nitrosopyrimidine when heated in the presence of a catalytic converter, the latter uses a nickel-aluminum alloy containing 45 - 53 weight. % Nickel and 47 - 55 wt.% aluminum, and the process is conducted in one stage in the presence of

25 водного раствора едкого натра или едкого кали. .25 aqueous solution of caustic soda or caustic potash. .

Примен емый сплав никел с гшюминием вл етс промышленным продуктом , выпускаемым отечественной и The nickel alloy with gsuminium used is an industrial product produced domestically and

Claims

30 foreign industry. Example: To a mixture of 25 g of 2 -4, b-diamino-5-yitro-pyrimidine, 70 g of a crushed nickel-aluminum alloy and 160 ml of water are added 50 ml of a 25% aqueous solution of sodium hydroxide, maintaining the temperature of the mixture not higher than 50 ° WITH. At the end of the addition of the alkali, the mixture is kept at this temperature for 1-1.5 hours, then boiled for 3-4 hours, filtered, the filtrate is acidified with sulfuric acid to a pH of .1, cooled and the precipitated triaminopyrimidine sulfate is separated. The yield of the target product 60 61%. Example2. To a mixture of 25 g of 2-TIO-4,6-diamino-5-nitrosopyrimidine, 70 g of crushed alloy of nickel and aluminum and 160 ml of water was added 50 ml of a 25% aqueous solution of potassium hydroxide, retaining the temperature in the mixture not higher than 50 - After completion of the alkali addition, the mixture is kept at 50 ° C for 1-1.5 hours, then boiled for 3 to 4 hours, filtered, the filtrate is acidified to pH 1 with sulfuric acid, cooled and the precipitated triaminopyrimidine sulfate is separated. The yield of the target product is 58–60%. The purity of the target product is established by the titration method (nitrimetry) and is 95–98%. Found,%: N 30.95 HQSO. Calculated,%: N, 31.40 (crystallization from water). Molecular weight 223. A thin layer of the chromatography in the system acetone: chloroform: 25% ammonia in a ratio of 8: 2: 1 on a forcefol of the UV-254 grade. Rf 0.4. Thus, carrying out the reaction at. normal pressure in the presence of an alloy of nickel and aluminum and iodine alkali reduces the explosion and fire hazards of the process, eliminates the stage of special preparation of the Rene catalyst, work with hydrogen under pressure, and also reduces the consumption of the alloy of nickel and aluminum by 3.5 times. An alloy of nickel and aluminum is an industrial product, so Ksus catalyst is a rene nickel prepared from this alloy of nickel and aluminum by treating the latter with an alkali immediately prior to use for reduction. The method of obtaining 4,5,6-triaminopyrimidine by reducing and desulfurizing 2-thio-4,6-diamino-5-nitrosopyrimidine in the presence of a catalyst with heating, characterized in that, in order to simplify the process, a nickel alloy is used as a catalyst. with aluminum, containing 45 - 53 weight. % nickel and 47 55 wt. % alcmini and the process is conducted in one stage in the presence of an aqueous solution of caustic soda or caustic potash. Sources of information taken into account in the examination 1. VM Berezovsky and AM Yurkevich Advanced synthesis of adenine. Journal of Organic Chemistry, 32, 1965 (1962).

2. USSR author's certificate 497296, cl. From 07 239/48, published 1974 (prototype).