104711-65-1

Basic information

• Product Name: 4-Chloro-2-cyano-6-methylpyrimidine
• Synonyms: 4-Chloro-2-cyano-6-methylpyrimidine;4-Chloro-2-cyano-6-methylpyridine;4-Chloro-6-Methylpicolinonitrile
• CAS NO: 104711-65-1
• Molecular Formula: C₇H₅ClN₂
• Molecular Weight: 152.583
• Mol File: 104711-65-1.mol
• Article Data: 9

Chemical Properties

• Melting Point: 78-79 °C
• Boiling Point: 250.1°C at 760 mmHg
• Flash Point: 105.1°C
• Appearance: /
• Density: 1.26g/cm³
• Vapor Pressure: 0.0221mmHg at 25°C
• Refractive Index: 1.554
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -1.72±0.10(Predicted)
• CAS DataBase Reference: 4-Chloro-2-cyano-6-methylpyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-2-cyano-6-methylpyrimidine(104711-65-1)
• EPA Substance Registry System: 4-Chloro-2-cyano-6-methylpyrimidine(104711-65-1)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 104711-65-1(Hazardous Substances Data)

Usage

General Description

4-Chloro-2-cyano-6-methylpyrimidine is a chemical compound with the molecular formula C6H4ClN3. It is a white to light yellow crystalline solid that is used in the synthesis of pharmaceuticals and agrochemicals. 4-Chloro-2-cyano-6-methylpyrimidine is a pyrimidine derivative, which is a class of heterocyclic compounds that are important in the field of medicinal chemistry. Its structure contains a chlorine atom, a cyano group, and a methyl group, which give it unique properties and potential biological activity. 4-Chloro-2-cyano-6-methylpyrimidine is used in the production of various drugs and pesticides, making it an important intermediate in the chemical industry.

InChI:InChI=1/C7H5ClN2/c1-5-2-6(8)3-7(4-9)10-5/h2-3H,1H3

Upstream product

• 5470-66-6 2-methyl-4-nitropyridine N-oxide 
• 3678-63-5 4-chIoro-2-methylpyridine 
• 696-08-2 4-chloro-2-picoline-N-oxide 
• 7677-24-9 trimethylsilyl cyanide 
• 79-44-7 N,N-Dimethylcarbamoyl chloride 

Downstream Products

• 1375338-67-2 2-(4-methoxy-6-methylpyridin-2-yl)-4-(3-methoxyphenyl)quinazoline 
• 1375324-82-5 2-(4-chloro-6-methylpyridin-2-yl)-4-(3-methoxyphenyl)quinazoline 
• 1375320-24-3 2-(4,6-dimethylpyridin-2-yl)-4-(3-methoxyphenyl)quinazoline 
• 1396337-04-4 N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide 
• 339586-00-4 1-(4-chloro-6-methylpyridin-2-yl)ethan-1-one 

Relevant articles and documents

Development and kilogram-scale synthesis of mGlu5 negative allosteric modulator VU0424238 (auglurant)

This communication details the kilogram-scale synthesis of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238, auglurant), a novel mGlu5 negative allosteric modulator (NAM) developed as an alternative treatment for depression. The process highlights a challenging pyridine N-oxidation sequence, an SNAr reaction, and the elimination of all chromatography steps (required in the medicinal chemistry route) with replacement by highly efficient recrystallizations (save one silica plug). The improved process was utilized for the preparation of a 1.2 kg toxicology batch, as well as a 2.82 kg GMP batch to support the Phase I trial, in very high purity (99.8%).

Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation

Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4.4 nM at a known allosteric binding site. Compound 27 had a clearance of 19.3 and 15.5 mL/min/kg in rats and cynomolgus monkeys, respectively. Imaging studies using a known mGlu5 PET ligand demonstrated 50% receptor occupancy at an oral dose of 0.8 mg/kg in rats and an intravenous dose of 0.06 mg/kg in baboons.

SUBSTITUTED 4-ALKOXYPICOLINAMIDE ANALOGS DS MGLUR5 NEGATIVE ALLOSTERIC MODULATORS

Disclosed are negative allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.