1193-24-4

Usage

Uses

Used in Organic Synthesis:
4,6-Dihydroxypyrimidine is used as a synthetic building block for the development of a wide range of organic compounds. Its chemical properties make it suitable for use in the synthesis of various molecules, including pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 4,6-Dihydroxypyrimidine is used as a key intermediate in the synthesis of various therapeutic agents. Its unique structure allows for the development of novel drugs with potential applications in treating a variety of diseases and medical conditions.
Used in Agrochemical Industry:
4,6-Dihydroxypyrimidine also finds application in the agrochemical industry, where it is used as a starting material for the synthesis of various agrochemicals, such as pesticides and herbicides. Its versatility in organic synthesis enables the development of new and effective products for agricultural use.
Used in Research and Development:
Due to its unique chemical properties, 4,6-Dihydroxypyrimidine is also utilized in research and development laboratories for the exploration of new chemical reactions and the synthesis of novel compounds. Its light yellow powder form makes it easy to handle and manipulate in various chemical processes.

Flammability and Explosibility

Notclassified

Synthesis

Synthesis of 4,6-dihydroxypyrimidine (DHP) by reaction of a malonic acid ester with formamide and an alkali metal alkoxide at elevated temperature.

InChI:InChI=1/C4H4N2O2/c7-3-1-4(8)6-2-5-3/h1-2H,(H2,5,6,7,8)

Synthetic route

malonic acid dimethyl ester (108-59-8) → 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
With sulfuric acid; sodium methylate; formamide In methanol; water	96%
With hydrogenchloride	76%
With hydrogenchloride; sodium methylate; formamide In methanol; water	75.1%
In water	74.8%

formamide (77287-34-4, 77287-35-5, 60100-09-6) + malonic acid dimethyl ester (108-59-8) → 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
With sodium methylate In methanol at 60 - 70℃; for 8h; Large scale;	90%
Stage #1: formamide; malonic acid dimethyl ester With sodium methylate In methanol at 95℃; for 1h; Stage #2: With hydrogenchloride In water at 35℃; pH=2.8; Temperature; pH-value; Reagent/catalyst; Solvent;	82.5%
With sodium methylate In methanol at 50℃; for 2h; Concentration; Temperature;

formamide (77287-34-4, 77287-35-5, 60100-09-6) + diethyl malonate (105-53-3) → 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
With methanol; sodium methylate for 3h; Reflux;	85%
With sodium ethanolate In ethanol at 65 - 110℃; for 49h;	82%
Stage #1: formamide With sodium In ethanol at 45℃; for 10h; Stage #2: diethyl malonate In ethanol at 65 - 110℃; for 4h;	67.9%

formamidine acetic acid (3473-63-0) + malonic acid dimethyl ester (108-59-8) → 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
Stage #1: formamidine acetic acid With sodium methylate In methanol at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: malonic acid dimethyl ester In methanol at 0℃; for 5h; Reflux;	62%

sodium ethanolate (141-52-6) + diethyl malonate (105-53-3) + formamidine (463-52-5) → 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
reagiert analog mit Propionamidin;

azoxystrobin (215934-32-0, 131860-33-8) → C21H15N3O5 + 2-(2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)acetic acid methyl ester + methyl (E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yl]oxyphenyl]-3-methoxyprop-2-enoate + 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
In methanol; water at 19℃; Quantum yield; Further Variations:; pH-values; UV-irradiation;
In methanol; water at 19℃; Quantum yield; Irradiation;

malonodiamide (108-13-4) + formic acid ethyl ester (109-94-4) → 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
With sodium ethanolate In ethanol Reflux;

acetamidine (143-37-3) + diethyl malonate (105-53-3) → 4,6-pyrimidinediol (1193-24-4)

Conditions	Yield
With sodium methylate In methanol at 0 - 25℃; for 18h;

Upstream product

• 141-52-6 sodium ethanolate 
• 105-53-3 diethyl malonate 
• 463-52-5 formamidine 
• 108-59-8 malonic acid dimethyl ester 
• 108-13-4 malonodiamide 
• 109-94-4 formic acid ethyl ester 
• 77287-34-4 formamide 
• 289-95-2 PYRIMIDINE 
• 3473-63-0 formamidine acetic acid 
• 1193-24-4 6-hydroxy-3,4-dihydropyrimidin-4-one 
• 143-37-3 acetamidine 
• 215934-32-0 azoxystrobin 

Downstream Products

• 138918-23-7 4,6-dihydroxy-5-benzylthiopyrimidine 
• 141764-36-5 5-phenylfuro<2,3-d>pyrimidin-4(3H)-one 
• 141764-35-4 5,6-dihydro-6-nitro-5-phenylfuro<2,3-d>pyrimidin-4(3H)one 
• 141764-46-7 5-(4-chlorophenyl)furo[2,3-d]pyrimidin-4(3H)-one 
• 141764-39-8 (5S,6S)-5-(4-Chloro-phenyl)-6-nitro-5,6-dihydro-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-44-5 5-(2-Chloro-phenyl)-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-37-6 (5R,6S)-5-(2-Chloro-phenyl)-6-nitro-5,6-dihydro-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-45-6 5-(3-Chloro-phenyl)-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-38-7 (5S,6S)-5-(3-Chloro-phenyl)-6-nitro-5,6-dihydro-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-49-0 5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4(3H)-one 
• 141764-42-3 (5S,6S)-5-(4-Methoxy-phenyl)-6-nitro-5,6-dihydro-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-42-3 (5S,6R)-5-(4-Methoxy-phenyl)-6-nitro-5,6-dihydro-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-48-9 5-(3-Methoxy-phenyl)-3H-furo[2,3-d]pyrimidin-4-one 
• 141764-41-2 (5S,6S)-5-(3-Methoxy-phenyl)-6-nitro-5,6-dihydro-3H-furo[2,3-d]pyrimidin-4-one 

Relevant academic research and scientific papers

Sustainable and cost-efficient electro-synthesis of formamidine acetate from cyanamide in aqueous acidic electrolyte

Formamidine represents a versatile building block in synthetic organic chemistry. We developed a new electrochemical synthesis of formamidine acetate by cathodic reduction of cyanamide in an aqueous electrolyte and in high yield. The crude product could be used for further conversions, such as to pyrimidines without purification. Compared to established synthetic routes neither prior processing of cyanamide was necessary, nor precious transition-metal catalyst were required, nor any reagent waste was produced, and only biocompatible and sustainable solvents were employed for this process, following the requirements ofgreen chemistry.

Photochemical transformations of 4,6-dihydroxypyrimidine and 2-methyl-4,6-dihydroxypyrimidine isolated in low-temperature Ar, Ne and H2 matrices

Monomers of 4,6-dihydroxypyrimidine and 2-methyl-4,6-dihydroxypyrimidine were trapped from the gas phase into low-temperature Ar, Ne and normal-H2 matrices. Dihydroxy and oxo-hydroxy tautomers were identified. The isolated monomers were exposed

Photochemical transformation of azoxystrobin in aqueous solutions

The photochemical behaviour of azoxystrobin fungicide (AZX) in water was studied under laboratory conditions. Photodegradation was initiated using a solar simulator (xenon arc lamp) or a jacketed Pyrex reaction cell equipped with a 125 W, high-pressure mercury lamp. HPLC/MS analysis (APCI and ESI in positive and negative modes) was used to identify AZX photoproducts. The calculated polychromatic quantum efficiencies (φ{symbol}) of AZX at pH 4.5, 7 and 9 were 5.42 × 10-3, 3.47 × 10-3 and 3.06 × 10-3 (degraded molecules per absorbed photon), respectively. The relatively narrow range of values indicates the stability of AZX with respect to photodegradation in the studied pH range. Results from the HPLC/MS analysis suggest that the phototransformation of AZX proceeds via multiple, parallel reaction pathways including: (1) photo-isomerization (E → Z), (2) photo-hydrolysis of the methyl ester and of the nitrile group, (3) cleavage of the acrylate double bond, (4) photohydrolytic ether cleavage between the aromatic ring giving phenol, and (5) oxidative cleavage of the acrylate double bond.

Production method of 4, 6-dihydroxypyrimidine

The invention belongs to the technical field of synthesis of 4, 6-dihydroxypyrimidine, and particularly relates to a production method of 4, 6-dihydroxypyrimidine, which comprises the following steps: a, performing cyclization reaction; b, cooling and dissolving; c, distilling alcohol under reduced pressure; d, performing acidification and separation; and e, washing and drying. The method provided by the invention not only improves the product content and yield, but also reduces the content of ammonia gas in recovered methanol, ensures the smooth proceeding of the main reaction, reduces the consumption of raw materials, solves the problems of large wastewater generation amount and difficult wastewater treatment, and has good economic and social benefits.

Preparation method of 4, 6-dihydroxypyrimidine

The invention provides a preparation method of 4, 6-dihydroxypyrimidine. The preparation method comprises the steps of carrying out a first-stage reaction, recovering reaction byproducts, carrying outa second-stage reaction, carrying out dissolving, recovering a solvent, and carrying out adsorbing. According to the preparation method, the raw materials comprise diester malonate, formamide and analkali metal alcoholate solution, and the mass content of the alkali metal alcoholate in the alkali metal alcoholate solution is 30%-50%. The preparation process of the 4, 6-dihydroxypyrimidine is a process of recovering a solvent by adopting normal-pressure reaction and negative-pressure distillation, and positive-pressure operation is avoided in the whole process on the premise of ensuring the yield and quality of the product, so that the preparation process is simple and easy to implement, and industrial production is easy to realize. According to the invention, a suitable sodium methoxideconcentration is selected according to the specific ratio relationship of dimethyl malonate, formamide and sodium methoxide, such that the material consumption is further reduced and the product yieldis improved on the premise of ensuring qualified product quality.

Pyrimidine hydrazone derivative and preparation method and application thereof

The invention relates to pyrimidine hydrazone derivatives as shown in a chemical structural formula I or II, pharmaceutically acceptable salts and pharmaceutical compositions thereof, and an application of the pyrimidine hydrazone derivatives and the pharmaceutically acceptable salts and the pharmaceutical compositions in preparation of influenza virus neuraminidase inhibitors, wherein X is selected from: fluorine, chlorine, bromine, hydroxyl, dihydroxy, 2-hydroxy-3-methoxy, 2-hydroxy-4-methoxy, 2-hydroxy-5-C1-C2 alkoxy, 2-hydroxy-6-C1-C2 alkoxy, 3-hydroxy-2-C1-C2 alkoxy, 3-hydroxy-4-C1-C2 alkoxy, 3-hydroxy-5-methyl C1-C2 alkoxy , 3-hydroxy-6-C1-C2 alkoxy, 4-hydroxy-2-C1-C2 alkoxy, 4-hydroxy-3-C1-C2 alkoxy, 4-hydroxy-3, 5-diC1-C2 alkoxy, trihydroxy or 4-hydroxy-3,5-dimethyl; and Y is selected from: fluorine, chlorine, bromine, acetamido, hydroxyl or methoxy.

4,6-dihydroxypyrimidine synthesizing method

The invention discloses a 4,6-dihydroxypyrimidine synthesizing method in the technical field of chemical synthesis. The synthesizing method comprises the following specific steps: S1: dissolving 10 to15g of dimethyl malonate into 300 to 500ml of a sodium methylate solution, heating and stirring evenly; S2: adding a catalyst into the solution, opening condensate water circulation to cool to normaltemperature and stirring for 15 to 20min; S3: utilizing constant-pressure dropping funnel to slowly dropwise adding 60 to 80ml of anhydrous triethylamine; S4: performing reduced pressure distillationto recycle a solvent and utilizing sodium hydroxide to adjust a pH value as 6 to7; S5: then performing suction filtration and extracting filtrate by an extracting agent; S6: obtaining 4,6-dihydroxypyrimidine. A preparation technology of the 4,6-dihydroxypyrimidine synthesizing method disclosed by the invention has the advantages of convenience, easiness and practicability; the 4,6-dihydroxypyrimidine synthesizing method has easiness in industrial production; furthermore, reactants can be completely reacted in a reaction process, a product yield can be improved, generation of reaction byproducts is reduced, varieties of mutation factors in the reaction process can be controlled, and quality stability of products is ensured.

Preparation method of 4,6-dihydroxypyrimidine

The invention provides a preparation method of 4,6-dihydroxypyrimidine. A bipolar membrane is applied to a preparation process of 4,6-dihydroxypyrimidine; 4,6-dihydroxypyrimidine reaction liquid formed in a preparation process of 4,6-dihydroxypyrimidine is treated by the bipolar membrane in advance before an acidification technology; during acidification, the consumption of acid liquid can be reduced obviously; besides, the wastewater quantity and a salt content in wastewater are also reduced, so that the environmental protection pressure is reduced; and the wastewater treatment cost is reduced.

Synthesis of 4,6-dichloropyrimidine and process optimization

The invention provides synthesis of 4,6-dichloropyrimidine and process optimization. The synthesis comprises the following main steps: (1) mixing dimethyl malonate and formamide, dripping the mixed solution into a sodium methylate-methanol solution, stirring, after the reaction is completed, distilling out methanol, recycling the methanol, further adding water to dissolve solid, continuously dripping diluted hydrochloric acid to adjust the pH value of the solution to be 2-3, leaving to stand, performing suction filtration, washing, and drying so as to obtain a product, that is, 4,6-dichloropyrimidine; (2) adding 4,6-dichloropyrimidine, trichloromethane and pyridine into a reaction kettle, stirring, slowly introducing phosgene, controlling the reaction temperature, after the reaction is completed, performing reduced pressure distillation to remove an excessive solvent trichloromethane so as to obtain a 4,6-dichloropyrimidine solution, performing suction filtration, concentrating, and crystallizing to obtain a white needle-shaped product, that is, 4,6-dichloropyrimidine. Compared with the prior art, the preparation method provided by the invention is simple, free of phosphorus-containing byproduct, and high in product yield and purity.

Discovery of triazolopyrimidine-based PDE8B inhibitors: Exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes

PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput screen was run with the goal of identifying selective tools for exploring the potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was particularly attractive since it was amenable to rapid deconstruction leading to inhibitors with very high ligand efficiency (LE) and lipophilic ligand efficiency (LLE). These triazolopyrimidines were optimized for potency, selectivity and ADME properties ultimately leading to compound 42. This compound was highly potent and selective with good bioavailability and advanced into pre-clinical development.