91591-63-8

Usage

Uses

Used in Pharmaceutical Industry:
2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE is used as a key intermediate in the synthesis of a selective muscarinic receptor 4 (M4) positive allosteric modulator called ML253. 2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE is a potent and brain penetrant agent that exhibits significant activity in preclinical models of schizophrenia, making it a valuable asset in the development of novel treatments for this mental disorder.
Additionally, due to its versatile chemical structure, 2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE can be further modified and utilized in the synthesis of other bioactive molecules with potential applications in various therapeutic areas, such as central nervous system disorders, cardiovascular diseases, and oncology. Its ability to form diverse chemical entities makes it a promising candidate for drug discovery and development efforts.

Synthesis

Phosphoryl chloride (973.2g), tetramethylammonium chloride (67.3g) and compound of Preparation 2 (227.1g) were added to dichloromethane (500g). The suspension was heated to 85°C and stirred for 5 hours. Excess of phosphoryl chloride was removed by distillation in vacuo. The reaction mixture was cooled below 30 °C and diluted with dichloromethane. The resulting solution was added to water (1350g) at room temperature and stirred for 30 minutes. The lower organic phase was separate and the aqueous phase extracted with dichloromethane. The organic phases were combined, washed with water and then treated with charcoal. The charcoal was filtered and a solvent swap to heptane was performed by distillation at atmospheric pressure. The solution was filtered at 50 °C and then cooled to 30 °C. On further cooling to 0°C crystals were obtained. These were isolated by filtration, washed twice with heptane. After drying at 50°C the desired product was obtained typically at 88-91 % . The above process was repeated with a reduction in dichloromethane during crystallisation and adding some methanol. The resulting plate-like crystals were more easily transferred for subsequent use.

InChI:InChI=1/C8H6Cl2N2/c1-4-6(3-11)8(10)12-5(2)7(4)9/h1-2H3

Upstream product

• 23819-92-3 5-chloro-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile 
• 123-54-6 acetylacetone 
• 1694-29-7 3-chloropentane-2,4-dione 
• 23819-92-3 5-chloro-2-hydroxy-4,6-dimethylnicotinonitrile 
• 769-28-8 2-hydroxy-4,6-dimethyl-3-carbonitrile 
• 769-28-8 3-Cyano-4,6-dimethyl-2(1H)-pyridon 

Downstream Products

• 1402714-41-3 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-2-hydroxy-3-methoxy-1-nitrobenzene 
• 923287-50-7 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide 
• 1391712-50-7 5-[3-(2,5-dichloro-4,6-dimethyl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-2-hydroxy-3-methoxy-1-nitrobenzene 
• 175204-44-1 2,5-dichloro-4,6-dimethylnicotinamide 

Relevant academic research and scientific papers

Preparation method of dichloro dialkyl fumaronitrile

The preparation method comprises the following steps: I raw materials are taken as raw materials, and chlorine or N - chlorosuccinimide is used as a chlorination reagent for chlorination reaction to generate compound II. The condensation reaction of compound II with cyanoacetamide is carried out under the action of a base to give compound III. The compound III is chlororeacted with phosphorus oxychloride to give a dichloro dialkyl nicotinonitrile. The preparation method avoids the use of sulfonyl chloride as a chlorination reagent, thereby avoiding the generation of sulfur dioxide tail gas, and preventing the generated acid waste gas from corroding equipment and the like.

Route Of Synthesis For Opicapone

The present invention relates to a new route of synthesis for obtaining Opicapone ((4Z)-4-[3-(2,5-dichloro-4,6-dimethyl-1-oxidopyridin-1-ium-3-yl)-2H-1,2,4-oxadia-zol-5-ylidene]-2-hydroxy-6-nitrocyclohexa-2,5-dien-1-one), new intermediates in the reaction path and the new substance 2,5-dichloro-N-hydroxy-4,6-dimethylpyridine-3-carboximidoyl chloride.

A structure-activity relationship study of the positive allosteric modulator LY2033298 at the M4 muscarinic acetylcholine receptor

Positive allosteric modulators (PAMs) targeting the M4 muscarinic acetylcholine receptor (mAChR) offer greater sub-type selectivity and unique potential as central nervous system agents through their novel mode of action to traditional orthosteric ligands. In an attempt to elucidate the molecular determinants of allostery mediated by the exemplar thienopyridine M4 mAChR PAM, LY2033298, we report herein a systematic structure-activity relationship (SAR) study investigating different linkage points, halogen replacements to examine size and electronic effects, and different substitution combinations on the thienopyridine scaffold. We applied an operational model of allosterism to determine values of functional affinity (KB), cooperativity (αβ) and intrinsic agonism (τB) for all compounds.

CHEMICAL COMPOUND USEFUL AS INTERMEDIATE FOR PREPARING A CATECHOL-O-METHYLTRANSFERASE INHIBITOR

There is disclosed a methylated intermediate which may be demethylated to provide an inhibitor of catechol-O-methyltransferase useful in the treatment of Parkinson's disease. Also disclosed are methods of making and using said intermediate.

Oxadiazole derivatives as COMT inhibitors

This invention relates to novel substituted [1,2,4]-oxadiazoles, their use in the treatment of some central and peripheral nervous system disorders, methods for their preparation and pharmaceutical compositions containing them.

Synthesis of some halogen- and nitro-substituted nicotinic acids and their fragmentation under electron impact

Features of electrophilic and nucleophilic substitution under chlorination and nitration reactions conditions have been investigated for 6-hydroxy- and 6-methyl-substituted derivatives of 3-cyano-4-methyl-2(1H)-pyridones. The polychloro- and nitro-substituted 3-cyano-4-methylpyridines obtained were used as synthons in the synthesis of some polyhalo- and nitro-substituted nicotinic acids and their amides. The fragmentation pathways of the synthesized compounds under electron impact have been studied.