CS223224B1 - Method of preparation of the 4-amino-1-/2,5-anhydro-beta-d-arabinofuranosyl/-pyridimin-2/1h/-on - Google Patents

Description

The present invention relates to a process for the preparation of 4-amino-1- (2,5-anhydro-β-D-arabinofurosyl) -pyrimidin-2 (1H) -one. The substance is an analogue of the natural nucleoside of the cytidine.

The starting material is [2R- (2a, 3 (3,3a _li d, 9a, 3a)] -2-chloromethyl-2,3,3a, 9a-tetrahydro-3-hydroxy-6-imino-6H-furo [2 '] hydrochloride. 3 ': 4,5] oxazolo [3,2-] pyrimidine, which is treated with a strongly basic ion exchanger, preferably in a carbonate cycle.

The product is isolated from the reaction mixture very simply by filtering the ion exchanger.

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The present invention provides a process for preparing 4-amino-1- (2,5-anhydro- [beta] -D-arabinofuranosyl) -pyrimidin-2 (1H) -one.

The essence of the process according to the invention is to give [2R- (2cr, 3, 3, 3a, 3a, 3a)] -2-chloromethyl-2,3,3a, 9a-tetrabydro-3-hydroxy-6 hydrochloride. -mino-6H-furo [2 ', 3']:

The 4,5-oxazolo [3,2-a] pyrimidine acts strongly with a basic ion exchanger, preferably in a carbonate cycle, and the product is isolated from the reaction mixture by filtering the ion exchanger, evaporating the filtrate, preferably under vacuum, and crystallizing the residue, preferably from water. [2R- (2a, 3 / 3,3a / 3,9a, 3 ') -2-chloromethyl-2,3,3a, 9a-tetrahydro-3-hydroxy-6-imino-6H-furo [2'] hydrochloride , 3 ': 4,5] oxazolo [3,2-] pyrimidine can be prepared by a known method (Collect. Czech. Chem. Commun. 1980, 45, 599; US Patent Certificates Nos. 199 949 and 204 212),

The process according to the invention can be carried out over a wide temperature range between 15 and 80 ° C, with a lower reaction temperature corresponding to a longer reaction time. Instead of a strongly basic ion exchanger in the carbonate cycle as a reagent, an alkali metal hydroxide solution such as sodium, potassium, lithium, or ammonia or a weakly basic ion exchanger in OH may be used. cycle.

The substance prepared according to the invention is a nucleic acid analogue and based on the tests carried out it can reasonably be expected that it can become a significant antimetabolite of nucleic acids and a representative of a new class of biologically highly active drugs similar to 5'-halogen derivatives (chlorine, bromine, iodine derivatives). and 5'-azido, 5'-O-methanesulfonyl and 5'-Op-toluenesulfonyl derivatives of both arabinosylcytosine and cyclocytidine.

In the following, the invention is explained in more detail by way of example without limiting it.

Example

[2R- (2a, 3 / 3,3a, 3,9a / 3] -2-chloromethyl-2,3,3a, 9a-tetrahydro-3-hydroxy-6-imino-6H- [2 ', 3': 4) hydrochloride 5] oxazolo [3,2-a] pyrimidine (2.80 g, 10 mmol) is dissolved in 200 ml of water, the solution is heated to 50 ° C, strongly basic ion exchange is added in the carbonate cycle [DOVEX 1.X8 (CO3) ² ")] and the reaction mixture is heated with stirring at 50 ° C for 6 h. The resin is then filtered off and washed with 0.5 L of water. total 1.72 grams (73%) of the product, 4-amino-1- (2,5-anhydro-β-D-arabinofuranosyl] pyrimidin-2 (1H) -one in the form of wire hemihy and mp 264-266 ° C (with decomposition), [α] 26 ^D = +233 degrees, (t = 0.50, water).

Claims (1)

Subject A process for the preparation of 4-amino-1- (2,5-anhydro- [3-D-amino-uranosyl) -pyrimidin-2- (1H) -one, characterized in that it is converted to the hydrochloride [2R- (2a, 3 / S, 3a / 3,9a (S) 1 -2-chloromethyl-2,3,3a, 9a-tetrahydro-3-hydroxy-6-imino-6H-furo [2 ', 3': 4,5] The oxazolo [3,2-a] pyrimidine has a strong basic ion exchanger of the invention, preferably in a carbonate cycle, and the product is isolated from the reaction by filtering the ion exchanger, evaporating the filtrate, preferably under vacuum, and crystallizing the residue, preferably from water.