45754-12-9

Basic information

• Product Name: 2,3-BIS(CHLOROMETHYL)PYRIDINE
• Synonyms: 2,3-BIS(CHLOROMETHYL)PYRIDINE;Pyridine, 2,3-bis(chloroMethyl)-
• CAS NO: 45754-12-9
• Molecular Formula: C₇H₇Cl₂N
• Molecular Weight: 176.04
• Mol File: 45754-12-9.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 264.48 ºC at 760 mmHg
• Flash Point: 139.294 ºC
• Appearance: /
• Density: 1.275 g/cm³
• Vapor Pressure: 0.016mmHg at 25°C
• Refractive Index: 1.548
• PKA: 2.94±0.22(Predicted)
• CAS DataBase Reference: 2,3-BIS(CHLOROMETHYL)PYRIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3-BIS(CHLOROMETHYL)PYRIDINE(45754-12-9)
• EPA Substance Registry System: 2,3-BIS(CHLOROMETHYL)PYRIDINE(45754-12-9)

Safety Data

• Hazardous Substances Data: 45754-12-9(Hazardous Substances Data)

Usage

General Description

2,3-Bis(chloromethyl)pyridine is a chemical compound with the molecular formula C7H7Cl2N. It is a chlorinated pyridine derivative that is primarily used as an intermediate in the synthesis of various pharmaceuticals and agrochemicals. 2,3-BIS(CHLOROMETHYL)PYRIDINE is known to have strong antimicrobial and antifungal properties, making it useful in the production of drugs and pesticides. It is also used as a building block in the synthesis of other organic compounds, due to its reactivity and ability to undergo various chemical reactions. However, 2,3-Bis(chloromethyl)pyridine is considered to be toxic and hazardous, and proper safety precautions should be taken when handling this substance.

InChI:InChI=1/C7H7Cl2N/c8-4-6-2-1-3-10-7(6)5-9/h1-3H,4-5H2

Synthetic route

2,3-bis(hydroxymethyl)pyridine hydrochloride (423169-40-8) → 2,3-bis(chloromethyl)-pyridine (45754-12-9)

Conditions	Yield
With thionyl chloride In toluene	89%

2,3-bis(hydroxymethyl)pyridine (38070-79-0) → 2,3-bis(chloromethyl)-pyridine (45754-12-9)

Conditions	Yield
With thionyl chloride In dichloromethane at 45℃; Cooling with ice;	40%
With thionyl chloride In dichloromethane at 75℃; for 1h;	26%
With thionyl chloride In dichloromethane Heating / reflux;	24%

2,3-diethyl pyridinedicarboxylate (2050-22-8) → 2,3-bis(chloromethyl)-pyridine (45754-12-9)

Conditions	Yield
With lithium aluminium tetrahydride; diethyl ether Erwaermen des Reaktionsprodukts mit Thionylchlorid;

Pyridine-2,3-dicarboxylic acid (89-00-9) → 2,3-bis(chloromethyl)-pyridine (45754-12-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 72 percent / conc. H2SO4 / 20 h / Heating 2: 85 percent / NaBH4 / ethanol / 17 h / Heating 3: 26 percent / SOCl2 / CH2Cl2 / 1 h / 75 °C View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid 2: sodium tetrahydroborate; hydrogenchloride / ethanol 3: thionyl chloride / toluene View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / Heating / reflux 2: sodium tetrahydroborate / ethanol; water / 20 °C 3: thionyl chloride / dichloromethane / Heating / reflux View Scheme

dimethyl 2,3-pyridinedicarboxylate (605-38-9) → 2,3-bis(chloromethyl)-pyridine (45754-12-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / NaBH4 / ethanol / 17 h / Heating 2: 26 percent / SOCl2 / CH2Cl2 / 1 h / 75 °C View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; hydrogenchloride / ethanol 2: thionyl chloride / toluene View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol; water / 20 °C 2: thionyl chloride / dichloromethane / Heating / reflux View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / 80 °C / Cooling with ice 2: thionyl chloride / dichloromethane / 45 °C / Cooling with ice View Scheme

2,3-Lutidine (583-61-9) → 2,3-bis(chloromethyl)-pyridine (45754-12-9)

2,3-bis(chloromethyl)pyridine hydrochloride (27221-49-4) → 2,3-bis(chloromethyl)-pyridine (45754-12-9)

Conditions	Yield
With sodium carbonate In dichloromethane; water pH=7.5 - 8;

2,3-bis(chloromethyl)-pyridine (45754-12-9) + trimethylsilyl cyanide (7677-24-9) → C9H7N3

Conditions	Yield
Stage #1: trimethylsilyl cyanide With cesium fluoride In acetonitrile at 10 - 20℃; for 0.5h; Stage #2: 2,3-bis(chloromethyl)-pyridine In acetonitrile at 10 - 40℃; for 12h; Temperature; Reagent/catalyst;	98.6%

2,3-bis(chloromethyl)-pyridine (45754-12-9) + sodium p-toluenesulfonamide (18522-92-4) → 6-(toluene-4-sulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (204593-50-0)

Conditions	Yield
In N,N-dimethyl-formamide at 70 - 80℃; for 2.5h;	80.5%

2,3-bis(chloromethyl)-pyridine (45754-12-9) + N-(((1S,9aS)-7-amino-3-oxo-1,3,9,9a-tetrahydrooxazolo[3,4-a]indol-1-yl)methyl)acetamide (1056039-93-0) → N-(((1S,9aS)-3-oxo-7-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-1,3,9,9a-tetrahydrooxazolo[3,4-a]indol-1-yl)methyl)acetamide (1056035-14-3)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 80 - 90℃;	80%

2,3-bis(chloromethyl)-pyridine (45754-12-9) + (S)-2-(6-methoxynaphthalen-2-yl)propanamide (72337-56-5, 123675-40-1, 134282-71-6, 134356-42-6) → 2-(6-methoxynaphthalen-2-yl)-1-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)propan-1-one (1558014-41-7)

Conditions	Yield
With sodium hydride In toluene at 80 - 90℃; for 5h;	70%

2,3-bis(chloromethyl)-pyridine (45754-12-9) → 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (147739-88-6)

Conditions	Yield
With methyl 2-(aminosulfonyl)benzoate; sodium hydride In N,N-dimethyl-formamide	46%

2,3-bis(chloromethyl)-pyridine (45754-12-9) + 4-fluorobenzoyl chloride (403-43-0) + 4-amino-N-(dimethylethyl)benzenesulfonamide (209917-48-6) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → N-(4-(N-tert-butylsulfamoyl)phenyl)-7-(4-fluorobenzoyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-6-carboxamide + N-(4-(N-tert-butylsulfamoyl)phenyl)-6-(4-fluorobenzoyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-7-carboxamide

Conditions	Yield
Stage #1: 2,3-bis(chloromethyl)-pyridine; 2-acetylaminomalonic acid diethyl ester With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 6.5h; Stage #2: With hydrogenchloride In water for 3h; Reflux; Stage #3: 4-fluorobenzoyl chloride; 4-amino-N-(dimethylethyl)benzenesulfonamide Further stages;	A 24 mg B 16%

2,3-bis(chloromethyl)-pyridine (45754-12-9) → 2,3-Lutidine (583-61-9)

Conditions	Yield
With methanol; palladium on activated charcoal; Lindlar's catalyst Hydrogenation;

Tetraisopropyl methylenediphosphonate (1660-95-3) + 2,3-bis(chloromethyl)-pyridine (45754-12-9) → [6-(Diisopropoxy-phosphoryl)-6,7-dihydro-5H-[1]pyrindin-6-yl]-phosphonic acid diisopropyl ester (104884-10-8)

Conditions	Yield
With sodium hydride 1.) DMSO, RT, 1 h 2.) 80 deg C, 1 h; Multistep reaction;

2,3-bis(chloromethyl)-pyridine (45754-12-9) + Tetraethyl methylenediphosphonate (1660-94-2) → [6-(Diethoxy-phosphoryl)-6,7-dihydro-5H-[1]pyrindin-6-yl]-phosphonic acid diethyl ester

Conditions	Yield
With sodium hydride 1.) DMSO, RT, 1 h 2.) 80 deg C, 1 h; Multistep reaction;

methanol (67-56-1) + 2,3-bis(chloromethyl)-pyridine (45754-12-9) + 4-methoxy-phenyl-sulphonyl chloride (98-68-0) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → methyl (+/-)-7-(4-methoxybenzenesulfonyl)-5,6,7,8-tetrahydro[1,7]naphthylidine-6-carboxylate + methyl (+/-)-6-(4-methoxybenzenesulfonyl)-5,6,7,8-tetrahydro[1,6]naphthylidine-7-carboxylate (523993-95-5)

Conditions	Yield
Multistep reaction;	A 200 mg B 1.00 g

methanol (67-56-1) + 2,3-bis(chloromethyl)-pyridine (45754-12-9) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → methyl (+/-)-5,6,7,8-tetrahydro[1,6]naphthylidine-7-carboxylate dihydrochloride + methyl (+/-)-5,6,7,8-tetrahydro[1,7]naphthylidine-6-carboxylate dihydrochloride

Conditions	Yield
Stage #1: 2,3-bis(chloromethyl)-pyridine; 2-acetylaminomalonic acid diethyl ester With sodium hydride In N,N-dimethyl-formamide at 20℃; for 14.5h; Stage #2: With hydrogenchloride for 3h; Heating; Stage #3: methanol With thionyl chloride for 20h; Heating; Title compound not separated from byproducts;

2,3-bis(chloromethyl)-pyridine (45754-12-9) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → ethyl 6-acetyl-7-ethoxycarbonyl-5,6,7,8-tetrahydro[1,6]naphthylidine-7-carboxylate + ethyl 7-acetyl-6-ethoxycarbonyl-5,6,7,8-tetrahydro[1,7]naphthylidine-6-carboxylate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 14.5h; Title compound not separated from byproducts;
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 6.5h;

2,3-bis(chloromethyl)-pyridine (45754-12-9) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → (+/-)-5,6,7,8-tetrahydro[1,7]naphthylidine-6-carboxylic acid dihydrochloride + (+/-)-5,6,7,8-tetrahydro[1,6]naphthylidine-7-carboxylic acid dihydrochloride

Conditions	Yield
Stage #1: 2,3-bis(chloromethyl)-pyridine; 2-acetylaminomalonic acid diethyl ester With sodium hydride In N,N-dimethyl-formamide at 20℃; for 14.5h; Stage #2: With hydrogenchloride for 3h; Heating; Title compound not separated from byproducts;

2,3-bis(chloromethyl)-pyridine (45754-12-9) → (+/-)-6-(4-methoxybenzenesulfonyl)-5,6,7,8-tetrahydro[1,6]naphthylidine-7-carboxylic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH / dioxane / 25 h / 20 °C View Scheme

2,3-bis(chloromethyl)-pyridine (45754-12-9) → 6,7-dihydro-5H-1-pyrindine-6,6-bisphosphonic acid (104884-01-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMSO, RT, 1 h 2.) 80 deg C, 1 h 2: 6N HCl / 2 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMSO, RT, 1 h 2.) 80 deg C, 1 h 2: 6N HCl / 2 h / Heating View Scheme

2,3-bis(chloromethyl)-pyridine (45754-12-9) + diethyl malonate (105-53-3) → diethyl 5,7‑dihydro‑6H‑cyclopenta[b]pyridine‑6,6‑dicarboxylate (220001-81-0)

Conditions	Yield
With sodium In ethanol for 5.08333h; Heating / reflux;

2,3-bis(chloromethyl)-pyridine (45754-12-9) + aspirin (50-78-2) → 2-acetyloxybenzoic acid 3-(nitrooxymethyl)-2-methylpyridinyl ester hydrochloride

2,3-bis(chloromethyl)-pyridine (45754-12-9) → 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine dihydrobromide

Conditions	Yield
Multi-step reaction with 2 steps 1: methyl 2-(aminosulfonyl)benzoate; sodium hydride / N,N-dimethyl-formamide 2: acetic acid; hydrogen bromide View Scheme

2,3-bis(chloromethyl)-pyridine (45754-12-9) → (4-difluoromethoxy-3-pyridin-2-ylethynyl-phenyl)-(5,7-dihydro-pyrrolo[3,4-b]pyridin-6-yl)-methanone (1253291-12-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: methyl 2-(aminosulfonyl)benzoate; sodium hydride / N,N-dimethyl-formamide 2.1: acetic acid; hydrogen bromide 3.1: 1-methyl-pyrrolidin-2-one; N-ethyl-N,N-diisopropylamine; 1,1'-carbonyldiimidazole / 1 h / 25 °C / Large scale 3.2: 4 h / 25 - 35 °C / Large scale View Scheme

2,3-bis(chloromethyl)-pyridine (45754-12-9) → C23H25NO6S2

Conditions	Yield
Multi-step reaction with 4 steps 1.1: cesium fluoride / acetonitrile / 0.5 h / 10 - 20 °C 1.2: 12 h / 10 - 40 °C 2.1: thionyl chloride / 12 h / 40 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / -20 - 10 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 0 - 10 °C View Scheme

2,3-bis(chloromethyl)-pyridine (45754-12-9) → C21H21NO6S2

Conditions	Yield
Multi-step reaction with 4 steps 1.1: cesium fluoride / acetonitrile / 0.5 h / 10 - 20 °C 1.2: 12 h / 10 - 40 °C 2.1: thionyl chloride / 12 h / 40 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / -20 - 10 °C 4.1: sodium carbonate / dichloromethane / 2 h / 0 - 30 °C View Scheme

2,3-bis(chloromethyl)-pyridine (45754-12-9) → C11H13NO4

Conditions	Yield
Multi-step reaction with 2 steps 1.1: cesium fluoride / acetonitrile / 0.5 h / 10 - 20 °C 1.2: 12 h / 10 - 40 °C 2.1: thionyl chloride / 12 h / 40 °C View Scheme

Upstream product

• 89-00-9 Pyridine-2,3-dicarboxylic acid 
• 38070-79-0 2,3-bis(hydroxymethyl)pyridine 
• 2050-22-8 2,3-diethyl pyridinedicarboxylate 
• 27221-49-4 2,3-bis(chloromethyl)pyridine hydrochloride 
• 423169-40-8 2,3-bis(hydroxymethyl)pyridine hydrochloride 
• 583-61-9 2,3-Lutidine 
• 605-38-9 dimethyl 2,3-pyridinedicarboxylate 

Downstream Products

• 583-61-9 2,3-Lutidine 
• 204593-50-0 6-(toluene-4-sulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine 
• 147739-88-6 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine 
• 1253291-12-1 (4-difluoromethoxy-3-pyridin-2-ylethynyl-phenyl)-(5,7-dihydro-pyrrolo[3,4-b]pyridin-6-yl)-methanone 
• 1211534-87-0 6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine 
• 523993-95-5 methyl (+/-)-6-(4-methoxybenzenesulfonyl)-5,6,7,8-tetrahydro[1,6]naphthylidine-7-carboxylate 

Relevant articles and documents

USP30 INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of USP30, and the treatment of USP30-mediated disorders.

A robust process for an mGluR5 negative allosteric modulator: Difluoromethylation and sonogashira coupling on large scale

The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd and Cu in the final API. Due to the relative nonpolar nature of the intermediates, water-miscible solvents were employed in all four steps to allow for direct crystallizations upon reaction completion. In addition, several crystalline morphologies of the API were discovered, and the isolation of the desired form II will be discussed.

ANTIMICROBIAL HETEROCYCLIC COMPOUNDS FOR TREATMENT OF BACTERIAL INFECTIONS

The present invention provides heterocyclic compounds of the following formula (I) : or pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof useful as antibacterial agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.