Production Method 1

113237-18-6

82671-02-1

Reaction Conditions

1.1 Reagents: Phosphorus oxychloride Catalysts: Triethanolamine ;  rt → 90 °C; 1 h, 80 - 90 °C
1.2 Reagents: Phosphorus pentachloride ;  20 h, reflux

Reference

Synthesis of 2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid

Tan, Zhen-you; et al, Huaxue Shiji, 2008, 30(1), 35-36

Production Method 2

75993-41-8

82671-02-1

Reaction Conditions

1.1 Reagents: Phosphorus pentachloride

Reference

Pyridonecarboxylic acids as antibacterial agents. VIII. An alternative synthesis of enoxacin via fluoronicotinic acid derivatives

Miyamoto, Teruyuki; et al, Chemical & Pharmaceutical Bulletin, 1987, 35(6), 2280-5

Production Method 3

74011-58-8

82671-02-1

Reaction Conditions

1.1 Reagents: Sodium ethoxide ,  Sodium 3-ethoxy-2-fluoro-3-oxoprop-1-en-1-olate Solvents: Ethanol
2.1 Reagents: Phosphorus pentachloride

Reference

Pyridonecarboxylic acids as antibacterial agents. VIII. An alternative synthesis of enoxacin via fluoronicotinic acid derivatives

Miyamoto, Teruyuki; et al, Chemical & Pharmaceutical Bulletin, 1987, 35(6), 2280-5

Production Method 4

113237-18-6

82671-02-1

Reaction Conditions

1.1 Reagents: Phosphorus trichloride

Reference

Synthesis and biological activity of fluorine-substituted pyridine-heterocyclic carboxylate compounds

Zheng, Hui; et al, Yingyong Huaxue, 2010, 27(2), 164-168

Production Method 5

75993-41-8

82671-02-1

Reaction Conditions

Reference

1,8-Naphthyridine derivatives and their salts

, Japan, , ,

Production Method 6

104866-50-4

82671-02-1

Reaction Conditions

1.1 Reagents: Ammonium bromide Catalysts: Zinc oxide (ZnO) Solvents: Xylene

Reference

Process for producing cyanopyridine derivative by reaction of 3-trichloromethylpyridine derivative with ammonium halide

, World Intellectual Property Organization, , ,

Production Method 7

109-94-4

107-91-5

82671-02-1

Reaction Conditions

1.1 Reagents: Sodium methoxide
2.1 Reagents: Phosphorus trichloride

Reference

Synthesis and biological activity of fluorine-substituted pyridine-heterocyclic carboxylate compounds

Zheng, Hui; et al, Yingyong Huaxue, 2010, 27(2), 164-168

Production Method 8

109-94-4

107-91-5

82671-02-1

Reaction Conditions

1.1 Reagents: Sodium methoxide
2.1 Reagents: Phosphorus pentachloride

Reference

Synthesis and biological activity of novel fluorine-containing pyridine-heterocyclic acylamide compounds

Zheng, Hui; et al, Nongyao, 2008, 47(1), 34-36

Production Method 9

109-94-4

107-91-5

82671-02-1

Reaction Conditions

1.1 Catalysts: Sodium methoxide Solvents: Toluene ;  rt; 1 h, < 50 °C
1.2 5 h, < 50 °C; 50 °C → 20 °C
1.3 Solvents: Methanol ;  10 - 20 °C; 20 °C → rt; 8 h, rt
1.4 Reagents: Acetic acid Solvents: Water ;  rt
2.1 Reagents: Phosphorus oxychloride Catalysts: Triethanolamine ;  rt → 90 °C; 1 h, 80 - 90 °C
2.2 Reagents: Phosphorus pentachloride ;  20 h, reflux

Reference

Synthesis of 2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid

Tan, Zhen-you; et al, Huaxue Shiji, 2008, 30(1), 35-36

Production Method 10

109-94-4

108-13-4

82671-02-1

Reaction Conditions

1.1 Reagents: Sodium ethoxide Solvents: Ethanol
1.2 Solvents: Ethanol
2.1 Reagents: Phosphorus pentachloride

Reference

Pyridonecarboxylic acids as antibacterial agents. VIII. An alternative synthesis of enoxacin via fluoronicotinic acid derivatives

Miyamoto, Teruyuki; et al, Chemical & Pharmaceutical Bulletin, 1987, 35(6), 2280-5

Production Method 11

105-39-5

82671-02-1

Reaction Conditions

1.1 Reagents: Potassium fluoride Catalysts: Tetrabutylammonium bromide Solvents: Dimethylformamide ;  rt → 120 °C; 15 min, 120 °C; 120 °C → 100 °C
1.2 10 h, reflux
2.1 Catalysts: Sodium methoxide Solvents: Toluene ;  rt; 1 h, < 50 °C
2.2 5 h, < 50 °C; 50 °C → 20 °C
2.3 Solvents: Methanol ;  10 - 20 °C; 20 °C → rt; 8 h, rt
2.4 Reagents: Acetic acid Solvents: Water ;  rt
3.1 Reagents: Phosphorus oxychloride Catalysts: Triethanolamine ;  rt → 90 °C; 1 h, 80 - 90 °C
3.2 Reagents: Phosphorus pentachloride ;  20 h, reflux

Reference

Synthesis of 2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid

Tan, Zhen-you; et al, Huaxue Shiji, 2008, 30(1), 35-36

2,6-Dichloro-5-fluoronicotinonitrile Raw materials

• Ethyl formate
• ethyl 2-chloroacetate
• 1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
• propanediamide
• 2-Cyanoacetamide
• 3-Cyano-2,6-dihydroxy-5-fluoropyridine
• 5-fluoro-1,2-dihydro-6-hydroxy-2-oxo-3-Pyridinecarboxamide
• PYRIDINE, 2,6-DICHLORO-3-FLUORO-5-(TRICHLOROMETHYL)-

2,6-Dichloro-5-fluoronicotinonitrile Preparation Products

• 2,6-Dichloro-5-fluoronicotinonitrile (82671-02-1)

• 1. Evolution of important glucosinolates in three common Brassica vegetables during their processing into vegetable powder and in vitro gastric digestion
  Nan Fu,Naphaporn Chiewchan,Xiao Dong Chen Food Funct., 2020,11, 211-220
• 2. Fatty acid eutectic mixtures and derivatives from non-edible animal fat as phase change materials?
  Pau Gallart-Sirvent,Marc Martín,Gemma Villorbina,Mercè Balcells,Aran Solé,Luisa F. Cabeza,Ramon Canela-Garayoa RSC Adv., 2017,7, 24133-24139
• 3. Embedding cyclic nitrone in mesoporous silica particles for EPR spin trapping of superoxide and other radicals?
  Eric Besson,Stéphane Gastaldi,Emily Bloch,Selma Aslan,Hakim Karoui,Olivier Ouari,Micael Hardy Analyst, 2019,144, 4194-4203
• 4. Esterase-responsive polymeric prodrug-based tumor targeting nanoparticles for improved anti-tumor performance against colon cancer?
  Gang Pan,Yi-jie Bao,Jie Xu,Tao Liu,Cheng Liu,Yan-yan Qiu,Xiao-jing Shi,Hui Yu,Ting-ting Jia,Xia Yuan,Ze-ting Yuan,Yi-jun Cao RSC Adv., 2016,6, 42109-42119
• 5. Evolution in surface coverage of CH3NH3PbI3?XClXvia heat assisted solvent vapour treatment and their effects on photovoltaic performance of devices
  Dhirendra K. Chaudhary,Pramendra Kumar,Lokendra Kumar RSC Adv., 2016,6, 94731-94738

Professional Introduction to 2,6-Dichloro-5-fluoronicotinonitrile (CAS No: 82671-02-1)

2,6-Dichloro-5-fluoronicotinonitrile, with the CAS number 82671-02-1, is a significant intermediate in the field of pharmaceutical and agrochemical research. This compound belongs to the nicotinonitrile class, characterized by its nitrile functional group and halogenated aromatic ring structure. The presence of both chlorine and fluorine substituents makes it a versatile building block for synthesizing more complex molecules with tailored biological activities.

The chemical structure of 2,6-Dichloro-5-fluoronicotinonitrile consists of a pyridine core substituted at the 2-position and 6-position with chlorine atoms, and at the 5-position with a fluorine atom. This specific arrangement imparts unique electronic and steric properties that are exploited in medicinal chemistry for designing novel therapeutic agents. The nitrile group at the 3-position further enhances its reactivity, allowing for various functionalization strategies such as hydrolysis to carboxylic acids or reduction to amides.

In recent years, 2,6-Dichloro-5-fluoronicotinonitrile has garnered attention in the development of bioactive compounds. Its scaffold is frequently used in the synthesis of kinase inhibitors, which play a crucial role in targeting various cancers and inflammatory diseases. For instance, derivatives of this compound have been investigated for their potential to inhibit tyrosine kinases, which are overexpressed in many malignancies. The fluorine atom, in particular, contributes to increased metabolic stability and binding affinity, making it an attractive moiety in drug design.

The agrochemical industry has also leveraged 2,6-Dichloro-5-fluoronicotinonitrile as a precursor in developing novel pesticides. Its structural features allow for the creation of compounds that exhibit potent activity against a broad spectrum of pests while maintaining environmental safety. Research has shown that certain nicotinonitrile derivatives derived from this intermediate exhibit insecticidal properties by targeting the nervous systems of pests, offering an alternative to traditional organophosphate-based insecticides.

Advances in synthetic methodologies have further expanded the utility of 2,6-Dichloro-5-fluoronicotinonitrile. Modern techniques such as transition-metal-catalyzed cross-coupling reactions have enabled efficient construction of complex molecular frameworks from this intermediate. These methods have been particularly valuable in accessing heterocyclic compounds with diverse pharmacological profiles. Additionally, computational chemistry approaches have been employed to predict the biological activity of derivatives before their synthesis, streamlining the drug discovery process.

The pharmacological potential of compounds derived from 2,6-Dichloro-5-fluoronicotinonitrile extends beyond oncology and agrochemical applications. Studies have explored its role in developing treatments for neurological disorders such as Alzheimer's disease and Parkinson's disease. The nitrile group has been shown to interact with specific enzymatic targets involved in neurodegeneration, suggesting that derivatives of this compound could modulate disease progression.

In conclusion, 2,6-Dichloro-5-fluoronicotinonitrile (CAS No: 82671-02-1) is a multifaceted compound with broad applications in pharmaceuticals and agrochemicals. Its unique structural features and reactivity make it a valuable intermediate for synthesizing bioactive molecules with potential therapeutic benefits. As research continues to uncover new synthetic strategies and biological functions, this compound is poised to remain a cornerstone in medicinal chemistry innovation.

• 34552-15-3(2-Chloro-3-fluoro-5-methylpyridine)
• 38186-84-4(2-Chloro-5-fluoro-3-methylpyridine)
• 873443-67-5(3-Pyridinecarbonitrile, 2,6-dichloro-4-(4-fluoro-2-methylphenyl)-)
• 1309371-71-8(2-Chloro-5,6-difluoronicotinonitrile)
• 820224-51-9(2,6-Dichloro-5-fluoro-3-(hydroxymethyl)pyridine)
• 474826-15-8(2-Chloro-5-fluoro-6-methylnicotinonitrile)
• 791644-48-9(2-chloro-5-fluoropyridine-3-carbonitrile)
• 1020253-14-8(6-Chloro-5-fluoronicotinonitrile)
• 104866-49-1(2,6-dichloro-3-fluoro-5-methyl-Pyridine)
• 948291-71-2(2-CHLORO-6-FLUOROQUINOLINE-3-CARBONITRILE)