18592-13-7

Basic information

• Product Name: 6-(Chloromethyl)uracil
• Synonyms: 6-Chloromethyl-1H-pyrimidine-2,4-dione;6-(Chloromethyl)uracil,98%;6-(chloroMethyl)-1,2,3,4-tetrahydropyriMidine-2,4-dione;2,4(1H,3H)-PyriMidinedione, 6-(chloroMethyl)-;Uracil, 6-(chloroMethyl)- (8CI);6-ChloroMethyluracil, 98.0%(T);3h)-pyrimidinedione,6-(chloromethyl)-4(1h;TIMTEC-BB SBB003961
• CAS NO: 18592-13-7
• Molecular Formula: C₅H₅ClN₂O₂
• Molecular Weight: 160.56
• EINECS: 242-431-9
• Product Categories: Heterocyclic Building Blocks;Pyrimidines;PyrimidinesHeterocyclic Building Blocks;Building Blocks;Halogenated Heterocycles
• Mol File: 18592-13-7.mol

Chemical Properties

• Melting Point: 257 °C (dec.)(lit.)
• Boiling Point: 493.9°C at 760 mmHg
• Flash Point: 252.5°C
• Appearance: /
• Density: 1.393g/cm³
• Vapor Pressure: 2.23E-10mmHg at 25°C
• Refractive Index: 1.511
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: almost transparency in N,N-DMF
• PKA: 7.91±0.10(Predicted)
• CAS DataBase Reference: 6-(Chloromethyl)uracil(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(Chloromethyl)uracil(18592-13-7)
• EPA Substance Registry System: 6-(Chloromethyl)uracil(18592-13-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 18592-13-7(Hazardous Substances Data)

Usage

Uses

Used in Medical Procedures:
6-(Chloromethyl)uracil is used as an alkali-resistant protein adsorbent in the medical industry. Its resistance to alkaline conditions makes it a valuable component in the development of materials and devices for protein separation, purification, and immobilization, which are essential processes in diagnostics, therapeutics, and research.
Used in Pharmaceutical Synthesis:
In the pharmaceutical industry, 6-(Chloromethyl)uracil is utilized in the synthesis of chlorophenyl hydroxypiperidine analogs. These analogs possess anti-amylatic activity, which means they can inhibit the activity of amylase enzymes. This property makes them potentially useful in the development of drugs for treating conditions related to abnormal amylase activity, such as diabetes or pancreatic disorders.

InChI:InChI=1/C5H5ClN2O2/c6-2-3-1-4(9)8-5(10)7-3/h1H,2H2,(H2,7,8,9,10)

Upstream product

• 110-86-1 pyridine 
• 41295-64-1 4-chloroacetoacetyl chloride 
• 57-13-6 urea 
• 89639-37-2 6-Chlormethyl-2-methylthio-pyrimidin-4(1H)-on 
• 638-07-3 ethyl (2-chloroaceto)acetate 
• 22126-44-9 6-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione 
• 626-48-2 6-Methyluracil 
• 36327-91-0 orotoaldehyde 
• 183205-42-7 6-(chloromethyl)-5-iodopyrimidine-2,4(1H,3H)-dione 
• 65-86-1 orotic acid 

Downstream Products

• 73541-61-4 6-p-Tolyloxymethyl-1H-pyrimidine-2,4-dione 
• 73541-63-6 6-(4-Allyl-2-methoxy-phenoxymethyl)-1H-pyrimidine-2,4-dione 
• 73541-58-9 6-(3-Chloro-phenoxymethyl)-1H-pyrimidine-2,4-dione 
• 73541-84-1 6-(o-Chlorphenoxymethyl)-uracil 
• 73541-62-5 6-(2-Isopropyl-5-methyl-phenoxymethyl)-1H-pyrimidine-2,4-dione 
• 73541-89-6 6-(2-Chloro-5-methyl-phenoxymethyl)-1H-pyrimidine-2,4-dione 
• 94820-33-4 6-<<(1-phenyl-1,2,3,4-tetrazol-5-yl)thio>methyl>uracil 
• 73541-45-4 6-[(4-Hydroxy-phenylamino)-methyl]-1H-pyrimidine-2,4-dione 
• 73541-85-2 α-(Uracil-6-methyl)-α-phenyl-essigsaeure-nitril 
• 73541-71-6 6-[(4-Chloro-phenylamino)-methyl]-1H-pyrimidine-2,4-dione 
• 73541-46-5 6-[(4-Methoxy-phenylamino)-methyl]-1H-pyrimidine-2,4-dione 
• 73541-53-4 4-[(2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidin-4-ylmethyl)-amino]-benzoic acid 
• 73541-51-2 2-[(2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidin-4-ylmethyl)-amino]-benzoic acid 
• 69774-56-7 2-(Uracil-6-methylthio)-essigsaeure 

Relevant articles and documents

Synthesis of a novel fused tricyclic heterocycle, pyrimido[5,4-e][1,4] thiazepine, and its derivatives

Sequential treatment of 5-bromo-2,4-dichloro-6-(chloromethyl)pyrimidine with 2-aminothiophenol and secondary amines afforded a series of 2-[(5-bromo-2-chloro-6-aminopyrimidin-4-yl)methylthio]aniline derivatives. Reaction of the latter compounds with secondary amines in ethanol gave a family of new 5,7-diamino-5,11-dihydropyrimido[5,4-e][1,4]benzothiazepines.

6-Substituted 5-fluorouracil derivatives as transition state analogue inhibitors of thymidine phosphorylase

A combination of mechanism-based and structure-based design strategies led to the synthesis of a series of 5- and 6-substituted uracil derivatives as potential inhibitors of thymidine phosphorlase/platelet derived endothelial cell growth factor (TP/PD-ECGF). Among those tested, 6-imidazolylmethyl-5- fluorouracil was found to be the most potent inhibitor with a K i-value of 51 nM, representing a new class of 5-fluoropyrimidines with a novel mechanism of action. Copyright Taylor & Francis, Inc.

Fragment-based approach to the design of 5-chlorouracil-linked-pyrazolo[1, 5-a][1,3,5]triazines as thymidine phosphorylase inhibitors

5-Chlorouracil-linked-pyrazolo[1,5-a][1,3,5]triazines were designed as new thymidine phosphorylase inhibitors based on the fragment based drug design approach. Multiple-step convergent synthetic schemes were devised to generate the target compounds. The intermediate 5-chloro-6-chloromethyluracil was synthesized by a 4-step reaction. A series of the second bicyclic intermediates, namely pyrazolo[1,5-a][1,3,5]triazin-2-thioxo-4-one, was obtained from various substituted 3-aminopyrazoles. These two intermediates were coupled finally in the presence of sodium ethoxide and methanol to yield the desirable target compounds. The methylthio coupling spacer was found to be suitable in enabling the interaction of the two fragments at the active site and allosteric site of the enzyme. The best coupled compound (9q) inhibited the thymidine phosphorylase with an IC50 value as low as 0.36 ± 0.1 μM. In addition, 9q demonstrated a mixed-type of enzyme inhibition kinetics, thus suggesting that it might indeed potentially bind at two different sites on the enzyme. Georg Thieme Verlag KG Stuttgart New York ISSN 0935-8943.

Purification method for uracil compound

The invention provides a purification method for a uracil compound, and belongs to the field of medical intermediate purification. The method comprises the steps that a uracil compound crude product obtained through preliminary purification is thermally dissolved in a polar aprotic solvent, a preliminarily purified uracil compound solid is precipitated through cooling and recrystallization, then an appropriate solvent is selected to carry out pulping on the uracil compound, pigment and other impurities contained in the uracil compound are dissolved, washed and dried to obtain the uracil compound with higher purity. The purification method for the uracil compound has the advantages that the uracil compound is purified by adopting an optimized recrystallization technology, the problem that the purification efficiency of a uracil compound in the prior art is low, in particular, the technical problem that a kilogram-level or tonnage-level of uracil compound in the prior art cannot be efficiently purified is solved, the production efficiency is improved, and the production cost is reduced.

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.

PROCESS FOR THE SYNTHESIS OF 6-CHLOROMETHYLURACIL

The invention relates to a process for the synthesis of 6-chloromethyluracil (6-(chloromethyl)pyrimidin-2,4(1H,3H)-dione) from ethyl 4-chloroacetoacetate and S- methylisothiourea hemisulfate via isolation of the novel intermediate 6- (chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one, and its subsequent treatment with aqueous sulfuric acid. Formula (I).

A 6 - chloromethyl uracil synthetic method (by machine translation)

The invention discloses a 6 - chloromethyl uracil synthetic method, comprises the following steps: (1) esterification reaction: the orotic adding anhydrous in methanol, adds by drops two chlorine Asia sulphone, reaction 6 hours, to evaporate the solvent, the organic solvent is added, stirring at the room temperature, filtered, and dried to get the orotic acid methyl ester; (2) reduction reaction: the methyl orotic dissolved in methanol, added to the Lewis acid, adding sodium borohydride, stirring at room temperature for 12 - 16 hours, ice for acetic acid neutralization, to evaporate the solvent, the organic solvent is added, stirring at the room temperature, filtering, drying, be 6 - hydroxy methyl uracil; (3) chlorinated reaction: the 6 - hydroxy methyl uracil in the added to the organic solvent, by adding thionyl chloride and a catalytic amount of N, N - dimethyl formamide, reaction 2 hours, cooled to the room temperature, filtering, drying, be 6 - chloro methyl uracil. Synthesis method of the invention, avoids the use of toxic reagents, mild reaction conditions, cheap, high yield, and is favorable for industrial production. (by machine translation)

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 tipiracil intermediate

The invention provides a preparation method of a tipiracil intermediate which is 6-(chloromethyl)-2, 4-(1H, 3H)-pyrimidinedione. 6-methyl-2, 4-(1H, 3H)-pyrimidinedione as an initial raw material undergoes an iodine replacement reaction at the 5th site of a compound and then the product undergoes reduction and chlorination reactions at the 6th site to produce a desired product. The preparation method has the advantages of stable processes, high yield and low cost and is suitable for industrial production.

Microwave promoted efficient synthesis of substituted uracils and thiouracils under solvent-free conditions

Several substituted uracils and thiouracils were synthesized in good yields by one-pot condensation reaction of methyl or ethyl β-ketoesters and urea (or thiourea) in solvent-free conditions under microwave irradiation and in short time.