CS261661B1 - A process for preparing 1-methyl-5H-diflaminoaracil - Google Patents

Abstract

The subject of the solution is a method of preparation of 1-methyl-5,6-diaminouracil-catalytic hydrogenation of 1-methyl-6mmino-5->nitrosouracil in aqueous alkaline pro-type. 1-Methyl-"•S^-diaminouracil is also used as a by-product for the preparation of purine tbases.

Description

The precursor of the invention is a method for the preparation of 1-methyl-5,6-diaminouracil of formula I

About

(i) NH,

0' · N/-j„ 1 c

CM _α 'JI which is an intermediate for the preparation of purine bases. The subject compound has been previously prepared by the reduction of l-methyl-5-nitroso-6-aminouracil of formula II

H-N' V

1.

Cl-L (II) dithionite sodium (Polonovski Bl 1946 80—83 J in the presence of ammonia (Timnis J. Chem. Soc. 1958 804), zinc in sulfuric acid (Ukai J. Pharm. Soc. Japan 74 674 1959), electrochemical reduction (Andosov Chim. Farm. Zh. 15 147 62—3), hydrogen sulfide (Jap. patent 59.210 896), or catalytically with hydrogen on Raney nickel in aqueous solution (Kudrlasov SSSR pat. 490 802 CA 84 P 74305]).

According to the process of the invention, the diaminouracil of formula I is prepared by catalytic hydrogenation of a nitroso derivative of formula II in a basic medium, where the nitroso derivative of formula II reacts with one or two equivalents of a base, depending on the amount of base. The practically water-insoluble nitroso derivative of formula II dissolves well in a basic medium and during hydrogenation, the catalyst is not covered by the nitroso derivative of formula II or the resulting diamine of formula I. This prevents the reduction of the active surface of the catalyst and the hydrogenation proceeds more quickly with good yield.

Sodium or potassium hydroxide, or an aqueous solution of ammonia, are used as bases. Hydrogenations are carried out at temperatures of 10 to 60 °C, preferably at 20 to 30 °C. Commonly used hydrogenation catalysts can be used as catalysts, e.g. palladium, platinum, nickel, cobalt, or these anchored on a carrier such as activated carbon, silica or other material with a large surface area, or Raney nickel or cobalt. Hydrogenation can be carried out, depending on the catalyst used, at atmospheric pressure or at a pressure of up to 12.0 MPa.

The advantage of the process according to the invention is that the hydrogenation is not stopped by coating the catalyst with the nitroso derivative of formula II or the diamine of formula I, since these are dissolved in the basic medium throughout the hydrogenation. The diamine of formula I is obtained in high purity and yield with minimal waste and with high volumetric efficiency.

In the following, the subject matter of the invention is explained by examples without being limited to these.

The structure of the hydrogenation products was confirmed by elemental analysis and comparison with the product obtained by an independent procedure by liquid chromatographic analysis.

Example 1 l-methyl-5,6-diaminouracil g l-methyl-6-amino-5-nitrosouracil is dissolved under cooling in a solution of 100 ml of water and 3.6 g of NaOH. 1.5 g of Raney nickel is added to the solution and the suspension is hydrogenated in a hydrogenation autoclave with stirring at a pressure of 4.0 MPa and a temperature of 25 °C for 2.5 h. After the hydrogenation is complete, the catalyst is filtered off and the filtrate is acidified with hydrochloric acid to a pH of 6.5-7.0. The precipitated product is filtered off with suction, washed with cold water and ethanol, and 12.7 g of l-methyl-5,6-diaminouracil (92 %), m.p. above 340 °C with decomposition, are obtained.

2B16S1

Example 2 — 10

g. compound of formula II g NaOH pressure MPa temperature time catalyst Extract 2 5.7 grams 2 grams 4.0 25°C 1.5 hours 0.5 g Pd/C 5% 53% 3 8.5 grams 3.5 grams 0.3 25°C 6 hours 1.5 g Ni (Raney) 65% 4 8.5 grams 4 grams 3.0 30°C 2 hours 0.3 g Pt/C 5% 93% 5 8.5 grams 4 grams 2.0 30°C 2 hours 0.3 g Pd/C 10% 92% 6 8.5 grams 2 grams 4.0 60°C 2 hours 1 g Pd/C 10% 82% 7 8.5 grams 2 grams 4.0 50°C 2 hours 1 g Pd/SiO ₂ , 5% 75% 8 8.5 grams 4 grams 4.0 20°C 3 hours 0.5 g palladium black 85% 9 8.5 grams A 0.3 50°C 6 hours 2 g Ni (Raney) 83% 10 8.5 grams B 3.0 20°C 2 hours 0.3 g Pd/C 10% 85%

A — 1-methyl-6-amino5-nitrosouracil was suspended in 50 ml of concentrated ammonia B — 5.6 g of KOH was used instead of NaOH

Claims (3)

A process for the preparation of 1-methyl-5,6-diaminoouracil of the formula I according to the invention by catalytic hydrogenation in aqueous solution, characterized in that the hydrogenation takes place in a basic medium, the molar ratio of nitroso derivative to base being 1: 0.8 to 1: 2. first 2. A process as claimed in claim 1, wherein the base used is sodium hydroxide, potassium hydroxide or aqueous ammonia. 3. The process of claim 1 wherein the reaction is carried out at a temperature of from 10 ° C to 60 ° C.