91591-63-8

Basic information

• Product Name: 2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE
• Synonyms: 2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE;2,5-DICHLORO-4,6-DIMETHYLPYRIDINE-3-CARBONITRILE;2,5-Dichloro-4,6-dimethylpyridine-3-carbonitrile, 3-Cyano-2,5-dichloro-4,6-dimethylpyridine;2,5-Dichloro-4,6-diMethyl-3-pyridinecarbonitrile;3-Cyano-2,5-dichloro-4,6-dimethylpyridine
• CAS NO: 91591-63-8
• Molecular Formula: C₈H₆Cl₂N₂
• Molecular Weight: 201.05
• Mol File: 91591-63-8.mol
• Article Data: 6

Chemical Properties

• Melting Point: 82 °C
• Boiling Point: 304.6 °C at 760 mmHg
• Flash Point: 138 °C
• Appearance: /
• Density: 1.36
• Vapor Pressure: 0.000867mmHg at 25°C
• Refractive Index: 1.564
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -2.79±0.10(Predicted)
• CAS DataBase Reference: 2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE(91591-63-8)
• EPA Substance Registry System: 2,5-DICHLORO-4,6-DIMETHYLNICOTINONITRILE(91591-63-8)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-36/37/39
• HazardClass: IRRITANT
• Hazardous Substances Data: 91591-63-8(Hazardous Substances Data)

Usage

Uses

2,5-Dichloro-4,6-dimethyl-3-pyridinecarbonitrile, can be used for the synthesis of a selective muscarinic receptor 4 (M4) positive allosteric modulator called ML253, which is a potent and brain penetrant compound that is active in a preclinical model of schizophrenia.

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

• 175204-44-1 2,5-dichloro-4,6-dimethylnicotinamide 
• 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 

Relevant articles and documents

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.

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.

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.