CS263369B1 - New 5-halogen-6-amino-1-methyluracil derivatives and process for preparing them - Google Patents

Abstract

The solution concerns new 5-halogen- -6-amino-1-methyluracil derivatives and the method for their preparation by reacting the 6-amino- -1-methyluracil and chlorine, alkaline hypochlorite metal or iodine in water; \ tor. \ t in organic solvents. Compounds serve as intermediates for preparation bases.

Description

The present invention provides novel 5-halo-6-amino-1-methyluracil derivatives of formula (I)

wherein X = Cl, J and a process for their preparation.

The subject compounds are prepared from 6-amino-1-methyluracil of formula IX

and the corresponding halogen, chlorine or iodine, optionally an alkali metal hypochlorite. The halogenations are carried out in an aqueous medium or in organic polar and non-polar solvents, or mixtures thereof, in an alkaline or acidic medium. Preferably, the halogenations in organic solvents are carried out in the catalytic presence of Lewis acids, e.g. boron trifluoride etherate. The temperature of the halogenations is between -10 and 60 ° C. Molar ratios of halogen to uracil of formula II of 1: 0.9 to 3: 1 are used.

The present compounds are important intermediates for the preparation of purine bases, e.g. theobromine, theophylline and caffeine.

In the following, the subject compounds are illustrated in the examples without being limited thereto.

Example 1

6-amino-5-chloro-l-methyl uracil

1.4 g (0.01 M) of 6-amino-2-methyluracil are suspended in 25 ml of dried dichloromethane.

1.85 ml of BF 4 are added to the suspension at 10 ° C, followed by the addition of 0.8 g of CO 2 while cooling and stirring. The reaction mixture is stirred for 1/2 hour. The solid was filtered off, washed with 2-3 ml of water, alcohol and dried. Yield: 1.19 g (70%) of 6-amino-5-chloro-1-methyluracil, mp 320 DEG-330 DEG C. with decomposition. N calculated 23.93 i, found 23.07%, Cl calculated 20.19% found 18.40%. M ⁺ 175 (in mass spectroscopy).

Example 2

6-amino-5-chloro-l-methyl uracil

2.8 g (0.02 M) of 6-amino-1-methyluracil are suspended in 50 ml of water while cooling at 3 to 5 ° C. To the suspension was added dropwise 52 ml of an aqueous solution containing 0.02 M sodium hypochlorite such that the temperature did not exceed 5 ° C. After the addition, the solution was stirred briefly and then concentrated HCl was added under cooling and the pH was adjusted to 3-4. The solid was filtered off with suction, washed with cold water until neutral. After drying, 2.9 g (74.2%) of 6-amino-5-chloro-1-methyluracil of m.p. 320 DEG-330 DEG C. with decomposition.

Example 3

6-amino-5-chloro-l-methyl uracil

2.8 g of 10.02 M) of 6-amino-1-methyluracil are dissolved in a solution of 50 ml of water and 1.6 g of NaOH. The solution is cooled to 10 ° C and 1.1 g of Cl _{2 are added.} After addition of chlorine, the solution is stirred for a short time, then concentrated HCl is added while cooling and the pH is adjusted to 3-4. into a neutral reaction. After drying, 1.9 g (54.1%) of 6-amino-5-chloro-1-methyluracil of mp 320-330 ° C with decomposition was obtained.

.Example 4

6-amino-5-chloro-l-methyl uracil

2.8 (0.02 M) of 6-amino-1-methyluracil was suspended in 25 mL of methanol and cooled to -1 to +2 ° C. 1.3 g of Cl2 are added to the suspension. After stirring briefly, the solid is filtered off with suction. 1.5 g (42.7 6-amino-5-chloro-1-methyluracil, m.p. 315 DEG-322 DEG C.) with decomposition were obtained.

Example 5

6-amino-5-chloro-1-methyluracy 1

2.8 g (0.02 M) of 6-amino-1-methyluracil is suspended in 50 ml of water. 1.4 g of CL · are added to the suspension, with stirring at such a rate that the temperature does not exceed 32 ° C. After addition of chlorine, the solid is filtered off with suction, washed with water until neutral and then with 20 ml of ethanol. It was obtained on 0.6 .mu.-β-amino-S-chloro-1-methyluracil (17.1%), m.p. 320 DEG-330 DEG C. with decomposition.

Example 6

6-amino-5-chloro-1-methyluracin

2.8 g (0.02 M) of 6-amino-1-methyluracil are suspended in 25 ml of 98% acetic acid and 4.2 g of chlorine are initially introduced into the suspension at 20 ° C at the beginning, and 50 ° C at the end of the addition. Stir 10 minutes after addition. The solid is filtered off with suction. 1.6 g (45.6%) of 6-amino-5-chloro-1-methyluracil of m.p. 318 DEG-325 DEG C. with decomposition.

Example 7

6-amino-5-iodo-l-methyl uracil

Using the procedure of Example 3, using 5.5 g of iodine (0.021 mol), 2.6 g of 6-amino-5-iodo-1-methyluracil of m.p. 275 ° C with decomposition. N calculated 15.74%, N found 16.02%, I calculated 47.52%, I found 46.88 i. The structure was further confirmed by spectral alleged.

Claims (8)

OBJECT OF THE INVENTION New 5-halo-6-amino-1-methyluracil derivatives of the general formula I O wherein X is chlorine or iodine. 2. A process for the preparation of a novel 5-chloro-6-amino-1-methyluracil according to item 1 of formula I, wherein X = Cl, characterized in that 1-methyl-6-aminoouracil of formula II (II) is reacted with chlorine or hypochlorite alkali metal. 3. A process for the preparation of a novel 5-iodo-6-amino-1-methyluracil according to claim 1, wherein X = J, characterized in that uracil II is reacted with iodine. 4. The process according to claim 2, wherein the halogenations are carried out in an aqueous medium, in organic polar and non-polar solvents, or in mixtures thereof. 5. Process according to claim 2 or 3, characterized in that the halogenations are carried out in an alkaline or acidic medium. 6. The process of claim 4, wherein the halogenations in organic solvents are carried out in the presence of Lewis acids as catalysts, e.g. boron trifluoride etherate. 7. Process according to claim 2, characterized in that the halogenations are carried out in a temperature range of -10 to 60 ° C. 8. A process according to claim 2, wherein the molar ratio of halogen to 6-amino-1-methyluracil of formula II is in the range of 1: 0.9 to 3: 1. Severography, n. p., MOST Price 2,40 Kčs