73742-45-7

Basic information

• Product Name: 2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI)
• Synonyms: 5-Chloro-6-(chloromethyl) pyrimidin-;5-chloro-6-(chloromethyl)-1H-pyrimidine-2,4-dione;2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI);2,4(1H,3H)-PyriMidinedione, 5-chloro-6-(chloroMethyl)-;5-chloro-6-(chloromethyl)-2,4(1H,3H)-Pyrimidinedione;Tipiracil Intermediates
• CAS NO: 73742-45-7
• Molecular Formula: C₅H₄Cl₂N₂O₂
• Molecular Weight: 195.005
• EINECS: 1592732-453-0
• Product Categories: HALOMETYL
• Mol File: 73742-45-7.mol

Chemical Properties

• Melting Point: 270-275 °C (decomp)
• Appearance: /
• Density: 1.63g/cm³
• Refractive Index: 1.583
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 5.73±0.10(Predicted)
• CAS DataBase Reference: 2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI)(73742-45-7)
• EPA Substance Registry System: 2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI)(73742-45-7)

Safety Data

• Hazardous Substances Data: 73742-45-7(Hazardous Substances Data)

Usage

Uses

Used in Medicinal Chemistry:
2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI) is used as a key intermediate in the synthesis of various drug molecules for its potential therapeutic applications. Its unique chemical structure allows for the development of novel compounds with improved pharmacological properties, enhancing their efficacy and safety in treating various diseases and conditions.
Used in Drug Development:
In the pharmaceutical industry, 2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI) is utilized as a building block for the design and synthesis of new drug candidates. Its potential biological activities and chemical properties make it a promising candidate for the development of innovative therapeutic agents with improved pharmacokinetics, pharmacodynamics, and reduced side effects.
Used in Scientific Research:
2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI) serves as an important research tool in the field of chemistry and biology. Its unique structure and potential applications provide valuable insights into the understanding of molecular interactions, biological processes, and the development of new therapeutic strategies. Researchers can leverage 2,4(1H,3H)-Pyrimidinedione,5-chloro-6-(chloromethyl)-(9CI) to explore its properties, mechanisms of action, and potential applications in various scientific disciplines.

InChI:InChI=1/C5H4Cl2N2O2/c6-1-2-3(7)4(10)9-5(11)8-2/h1H2,(H2,8,9,10,11)

Upstream product

• 50610-49-6 5,5-dichloro-6-hydroxy-6-methyl-5,6-dihydrouracil 
• 7647-01-0 hydrogenchloride 
• 18592-13-7 6-chloromethyluracil 
• 626-48-2 6-Methyluracil 
• 36327-91-0 orotoaldehyde 
• 22126-44-9 6-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione 
• 88-00-6 ethyl 2,4-dichloro-3-oxobutanoate 
• 57-13-6 urea 
• 65-86-1 orotic acid 
• 6153-44-2 methyl orotate 
• 91447-90-4 methyl 5-chloro-2,6-dioxo-3H-pyrimidine-4-carboxylate 

Downstream Products

• 183204-74-2 Tipiracil 
• 16018-87-4 5-chloro-6-methyluracil 

Relevant articles and documents

Design of Novel Inhibitors of Human Thymidine Phosphorylase: Synthesis, Enzyme Inhibition, in Vitro Toxicity, and Impact on Human Glioblastoma Cancer

Overexpressed human thymidine phosphorylase (hTP) has been associated with cancer aggressiveness and poor prognosis by triggering proangiogenic and antiapoptotic signaling. Designed as transition-state analogues by mimicking the oxacarbenium ion, novel pyrimidine-2,4-diones were synthesized and evaluated as inhibitors of hTP activity. The most potent compound (8g) inhibited hTP in the submicromolar range with a noncompetitive inhibition mode with both thymidine and inorganic phosphate substrates. Furthermore, compound 8g was devoid of apparent toxicity to a panel of mammalian cells, showed no genotoxicity signals, and had low probability of drug-drug interactions and moderate in vitro metabolic rates. Finally, treatment with 8g (50 mg/(kg day)) for 2 weeks (5 days/week) significantly reduced tumor growth using an in vivo glioblastoma model. To the best of our knowledge, this active compound is the most potent in vitro hTP inhibitor with a kinetic profile that cannot be reversed by the accumulation of any enzyme substrates.

Potential tumor-selective nitroimidazolylmethyluracil prodrug derivatives: Inhibitors of the angiogenic enzyme thymidine phosphorylase

Thymidine phosphorylase (TP) is an angiogenic growth factor and a target for anticancer drug design. Molecular modeling suggested that 2′-aminoimidazolylmethyluracils would be potent inhibitors of TP. The novel 5-halo-2-amino-imidazolylmethyluracils (4b/4c) were very potent inhibitors of E. coli TP (IC50 ～ 20 nM). Contrastingly, the corresponding 2′-nitroimidazolylmethyluracil (as bioreductively activated) prodrugs (3b/3c) were 1000-fold less active (IC50 22-24 μM. This approach may be used to selectively deliver TP inhibitors into hypoxic regions of solid tumors where TP is overexpressed.

Synthesis and evaluation of 6-methylene-bridged uracil derivatives. Part 1: Discovery of novel orally active inhibitors of human thymidine phosphorylase

A series of novel 6-methylene-bridged uracil derivatives have been prepared as inhibitors of human thymidine phosphorylase (TP). To enhance the in vivo antitumor activity of fluorinated pyrimidine 2′-deoxyribonucleosides such as 2′-deoxy-5-(trifluoromethyl)uridine (F3dThd), a potent TP inhibitor preventing their degradation to an inactive compound, has become a target of medicinal chemistry. We present here the synthesis and evaluation of novel human TP inhibitors. Introduction of an N-substituted aminomethyl side chain at the 6-position of 5-chlorouracil has improved water solubility and enhanced inhibitory activity compared with the known TP inhibitor, 6-amino-5-chlorouracil. Compound 42 was reasonably well absorbed in mice after oral administration. When combined with F3dThd, compound 42 exerted its TP inhibitory potency by increasing the maximum plasma concentrations of the former as evidenced in experiments with monkeys. Positive changes in pharmacokinetic profile were accompanied by the enhanced in vivo antitumor activity of this combination when compared to F3dThd alone, in mice bearing human tumor xenografts. Both biochemical and pharmacological effects appeared to fit the concept as anticipated.

AN IMPROVED PROCESS FOR THE PREPARATION OF TIPIRACIL HYDROCHLORIDE AND INTERMEDIATES THEREOF

The present invention provides a process for the preparation of Tipiracil HCl of Formula (I) and intermediate thereof with improved yields and purities.

PROCESS FOR THE PREPARATION OF TIPIRACIL HYDROCHLORIDE

The present invention relates to a process for preparation of tipiracil of formula (I) or salt thereof.

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.

SUBSTITUTED PYRROLOPYRIDINES AS ATR INHIBITORS

The disclosure includes compounds of Formula (I) wherein A, W, m, R5, R6, R7, and R8, are defined herein. Also disclosed is a method for treating a neoplastic disease with these compounds.

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.

Tipiracil hydrochloride and synthesis method of intermediate 6-(chloromethyl)uracil

The invention provides a synthesis method of 6-(chloromethyl)uracil. The synthesis method comprises the steps that 6-(methyl)uracil and copper oxide perform oxidizing reaction in a solvent to obtain 6-(formyl)uracil; the 6-(formyl)uracil is reduced to obtain 6-(hydroxymethyl)uracil; the 6-(hydroxymethyl)uracil is subjected to chlorination to obtain the 6-(chloromethyl)uracil, wherein the purity of the 6-(chloromethyl)uracil is high than 99.0%. The synthesis method of the 6-(chloromethyl)uracil is optimized, selenium dioxide is replaced by low-toxicity metal oxide to achieve a 6-(formyl)uracil oxidation process, environmental friendliness is improved, and meanwhile the yield and purity of the 6-(chloromethyl)uracil are improved. The invention further provides a synthesis method of tipiracil hydrochloride. The obtained 6-(chloromethyl)uracil obtained by adopting the process is an intermediate, the tipiracil hydrochloride is directly prepared through three steps of chloro, condensing and salifying reaction, the obtained raw material drug does not need any purifying process, and the purity ishigher than 99.0%.

Preparation method of 5-chloro-6-(chloromethyl)-2,4-(1H,3H)-pyrimidinedione

The patent provides a preparation method of 5-chloro-6-(chloromethyl)-2,4-(1H,3H)-pyrimidinedione. Orotic acid, which is used as a starting material, undergoes alpha-hydrogen chlorination; then, carboxyl is directly reduced to hydroxymethyl; and a chlorination replacement reaction is carried out. Through the three-step reactions, the target product is obtained. The preparation method of the invention is simple to operate, has stable process, has high yield, is low-cost, and is suitable for industrial production.