183204-74-2

Usage

Uses

Used in Pharmaceutical Industry:
5-Chloro-6-((2-iminopyrrolidin-1-yl)methyl)pyrimidine-2,4(1H,3H)-dione is used as an active pharmaceutical ingredient for the treatment of advanced or relapsed unresectable colorectal cancer. It is administered in combination with trifluridine, a nucleoside metabolic inhibitor, to enhance the therapeutic effects and improve patient outcomes.
The compound's application in the treatment of colorectal cancer is based on its ability to target and inhibit specific cellular processes involved in cancer cell growth and proliferation. By combining it with trifluridine, the overall effectiveness of the treatment is increased, providing a more comprehensive approach to managing this type of cancer.

Upstream product

• 626-48-2 6-Methyluracil 
• 36327-91-0 orotoaldehyde 
• 2101241-71-6 5-chloro-6-(2-oxopyrrolidin-1-yl)methyl-2,4-(1H,3H)pyrimidinedione 
• 18592-13-7 6-chloromethyluracil 
• 73742-45-7 5-chloro-6-(chloromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione 
• 872-34-4 2-imino-pyrrolidine 
• 6153-44-2 methyl orotate 
• 91447-90-4 methyl 5-chloro-2,6-dioxo-3H-pyrimidine-4-carboxylate 
• 7544-75-4 2-iminopyrrolidine-hydrochloride 

Relevant academic research and scientific papers

Synthesis and evaluation of 6-methylene-bridged uracil derivatives. Part 2: Optimization of inhibitors of human thymidine phosphorylase and their selectivity with uridine phosphorylase

A series of novel 6-methylene-bridged uracil derivatives have been optimized for clinical use as the inhibitors of human thymidine phosphorylase (TP). We describe their synthesis and evaluation. Introduction of a guanidino or an amidino group enhanced the in vitro inhibitory activity of TP comparing with formerly reported inhibitor 1. Their selectivity for TP based on uridine phosphorylase inhibitory activity was also evaluated. Compound 2 (TPI) has been selected for clinical evaluation based on its strong TP inhibition and excellent modulation of 2′-deoxy-5-(trifluoromethyl)uridine (F3dThd) pharmacokinetics. As a result, TAS-102 (a combination of F3dThd and TPI) is currently in phase 1 clinical studies.

METHOD FOR DETECTING TRIFLURIDINE- AND/OR TIPIRACIL-RELATED SUBSTANCE

This invention provides a method that is capable of detecting a trifluridine-related substance and a tipiracil-related substance contained in a sample containing trifluridine or a salt thereof and tipiracil or a salt thereof using the same procedure. The method is for detecting a trifluridine-related substance or a tipiracil-related substance or both, the method comprising the step of subjecting a sample containing trifluridine or a salt thereof and tipiracil or a salt thereof to high-performance liquid chromatography using a mobile phase composed of an organic phase and an aqueous phase.

PROCESS FOR PREPARING CRYSTALLINE TIPIRACIL HYDROCHLORIDE

The present invention relates to a process for the preparation of Tipiracil hydrochloride crystal III, which comprises reaction of Tipiracil with hydrochloric acid in presence of solvent is selected from alcohol and/or water. Further, the present invention relates to pure Tipiracil base having purity greater than about 99.0% by HPLC.

SOLID STATE FORMS OF 5-CHLORO-6-[(2-IMINOPYRROLIDIN-1-YL)METHYL]PYRIMIDINE-2,4-(1H,3H)-DIONE HYDROCHLORIDE AND THEIR PROCESSES FOR THE PREPARATION THEREOF

The present invention relates to solid state forms of 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]pyrimidine-2,4-(1H,3H)-dione hydrochloride compound of formula-1a and their processes for the preparation thereof and an improved process for the preparation of 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]pyrimidine-2,4-(1H,3H)-dione hydrochloride. The present inventors also provides an amorphous polymorph of the combination drug consisting of 2'-deoxy-5-(trifluoromethyl) uridine and 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]pyrimidine-2,4-(1H,3H)-dione monohydrochloride and its process for the preparation.

5 - Chloro -6 - [(2 - imino -1 - pyrrolidine) methyl] - 2, 4 (1 H, 3 H) - dione or its salt preparation method

The invention provides a preparation method of 5-chloro-6-[(2-imino-1-pyrrolidinyl)methyl]-2,4(1H,3H)-pyrimidine dione or salts thereof, which comprises the following steps: by using 6-methylpyrimidyl-2,4(1H,3H)-dione as an initial raw material, carrying out 6- site methyl oxidation and 5- site hydrogen chlorination, reducing the 6- site formyl group, carrying out condensation with 2-aminopyrrolidine or corresponding salts to obtain the target product. The method is simple to operate and stable in technique, is suitable for industrial production, and has the advantages of high yield, high purity and low cost.

Tipracil intermediate, and preparation methods of tipracil intermediate, tipracil and tipracil hydrochloride

The invention relates to the field of medicine synthesis, in particular to a pyrimidine type derivative, particularly a tipracil intermediate, and preparation methods of the tipracil intermediate, tipracil and tipracil hydrochloride. The preparation method of the tipracil intermediate comprises the following step that 5-chloro-6-methoxycarbonyl uracil is subjected to reductionr eaction to obtain 5-chloro-6-hydroxymethyl uracil; chloro-6-methoxycarbonyl uracil is used for obtaining the 5-chloro-6-methoxycarbonyl uracil through reduction and hydroxyl chloro reaction. The oxidizaiton step in the prior art and a deadly poisonous compound of selenium dioxide are avoided, so that the meidcine qualiyt safety is fundamentally ensured. The reaction conditions of the reductionr eaction are mild; the production cost is reduced. In addition, the yield of final products and middle products in the method is high; the separation purification is easy; the purity is high. The method provided by the invention has the advantages that the raw materials can be easily obtained; the operation is simple; the environment-friendly efefct is good; the process is stable; the method is suitable for industrial production, and the like.

Preparation method of tipiracil

The invention discloses a preparation method of tipiracil. The method comprises the following steps: by using 6-chloromethyl uracil as the initial raw material, carrying out chlorination reaction to obtain an intermediate A, carrying out condensation reaction on the intermediate A and alpha-pyrrolidone in the presence of strong alkali to enhance the reaction selectivity, and finally, carrying out ammonolysis reaction on the intermediate B to obtain the tipiracil. The preparation method is simple, has the advantages of mild reaction conditions and high product purity, and is suitable for industrial production.