113-92-8

Basic information

• Product Name: Chlorpheniramine maleate
• Synonyms: 1-(p-Chlorophenyl)-1-(2-pyridyl)-3-dimethy-laminopropanebimaleate;1-(p-chlorphenyl)-1-(2-pyridyl)-3-dimethylaminopropanmaleat;2-(p-chloro-alpha-(2-(dimethylamino)ethyl)benzyl)-pyridinmaleate(1:1);allerclor;allergin;alunex;antagonate;carbinoxamidemaleate
• CAS NO: 113-92-8
• Molecular Formula: C₄H₃O₄*C₁₆H₂₀ClN₂
• Molecular Weight: 390.86
• EINECS: 205-054-0
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Antagonists;Histaminergics;Neurotransmitters;TELDRIN;API
• Mol File: 113-92-8.mol

Chemical Properties

• Melting Point: 130-135 °C(lit.)
• Boiling Point: 379 ºC at 760 mmHg
• Flash Point: 9℃
• Appearance: White crystalline powder
• Density: 1.1984 (rough estimate)
• Vapor Pressure: 2.9E-14mmHg at 25°C
• Refractive Index: 1.6800 (estimate)
• Storage Temp.: -20°C Freezer
• Solubility: Freely soluble in water, soluble in ethanol (96 per cent)
• Water Solubility: 1-5 g/100 mL at 21 ºC
• Merck: 14,2180
• CAS DataBase Reference: Chlorpheniramine maleate(CAS DataBase Reference)
• NIST Chemistry Reference: Chlorpheniramine maleate(113-92-8)
• EPA Substance Registry System: Chlorpheniramine maleate(113-92-8)

Safety Data

• Hazard Codes: T,F
• Statements: 25-39/23/24/25-23/24/25-11
• Safety Statements: 36/37/39-45-36/37-16
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: US6504000
• TSCA: Yes
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 113-92-8(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 113-92-8 differently. You can refer to the following data:
1. An antagonist of the histamine H1-receptor
2. Antihistaminic
3. (±)-Chlorpheniramine maleate salt has been used:as H1 receptor antagonist to determine the receptor functionto block the effect of compound 48/80 on plasma IGF-Ias a standard for fast sensing and determination by sequential injector coupled with potentiometer

Brand name

Trimeton (Schering-Plough); Teldrin (GlaxoSmithKline).

General Description

Different sources of media describe the General Description of 113-92-8 differently. You can refer to the following data:
1. Chlorpheniraminemaleate, (±)2-[p-chloro-α-[2-dimethylamino)ethyl]benzyl]pyridine bimaleate (Chlor-Trimeton), is a white crystallinepowder that is soluble in water (1:3.4), in alcohol(1:10), and in chloroform (1:10). It has a pKa of 9.2, and anaqueous solution has a pH between 4 and 5. Chlorination ofpheniramine in the para position of the phenyl ring increasespotency 10-fold with no appreciable change in toxicity.Most of the antihistaminic activity resides with thedextro isomer (see under “Dexchlorpheniramine Maleate” ).The usual dose is 2 to 4 mg 3 or 4 times a day. It has a halflifeof 12 to 15 hours.
2. Odorless white crystalline solid or white powder with a bitter taste. pH (2% aqueous solution) 5. pH (1% aqueous solution) 4-5.

Air & Water Reactions

Water soluble.

Reactivity Profile

A halogenated amine, ester. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. Esters react with acids to liberate heat along with alcohols and acids. Strong oxidizing acids may cause a vigorous reaction that is sufficiently exothermic to ignite the reaction products. Heat is also generated by the interaction of esters with caustic solutions. Flammable hydrogen is generated by mixing esters with alkali metals and hydrides.

Fire Hazard

Flash point data for Chlorpheniramine maleate are not available; however, Chlorpheniramine maleate is probably combustible.

Biochem/physiol Actions

Chlorpheniramine maleate (CPM) can prevent rhinitis and urticaria. It is used to cure several allergic conditions. This antihistamine is used in small-animal veterinary practices.

Safety Profile

Poison by ingestion, intravenous, and subcutaneous routes. Experimental reproductive effects. Used as an antihistamine. Mutation data reported. When heated to decomposition it emits very toxic fumes of Cland NOx.

Veterinary Drugs and Treatments

Antihistamines are used in veterinary medicine to reduce or help prevent histamine mediated adverse effects. Chlorpheniramine is one the more commonly used antihistamines in the cat for the treatment of pruritus. It may also be of benefit as a mild sedative in small animals due to its CNS depressant effects.

Dosage forms

4 to 6 mg PO q4–6h. Maximum daily dose is 24 mg for adults and children 12 years or older. Found frequently in combination with acetaminophen and pseudoephedrine.

InChI:InChI=1/C16H19ClN2.C4H4O4/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13;5-3(6)1-2-4(7)8/h3-9,11,15H,10,12H2,1-2H3;1-2H,(H,5,6)(H,7,8)

Synthetic route

formic acid (64-18-6) + Didesmethylchlorpheniramine (20619-13-0) + maleic acid (110-16-7) → chlorphenamine maleate (113-92-8)

Conditions	Yield
Stage #1: formic acid; Didesmethylchlorpheniramine In water; N,N-dimethyl-formamide at 100℃; for 24h; Stage #2: maleic acid In isopropyl alcohol at 80℃; for 2h;	88.8%

2-(4-chlorobenzyl)pyridine (4350-41-8) + 2-(dimethylamino)ethyl chloride (107-99-3) + maleic acid (110-16-7) → chlorphenamine maleate (113-92-8)

Conditions	Yield
Stage #1: 2-(4-chlorobenzyl)pyridine With sodium amide In toluene Reflux; Stage #2: 2-(dimethylamino)ethyl chloride In toluene for 6h; Reflux; Stage #3: maleic acid In water	54.4%
Stage #1: 2-(4-chlorobenzyl)pyridine With sodium amide In toluene Reflux; Stage #2: 2-(dimethylamino)ethyl chloride In toluene for 6h; Reflux; Stage #3: maleic acid In toluene	22.4 g

p-chlorobenzyl cyanide (140-53-4) → chlorphenamine maleate (113-92-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: cobaltocene / 4 h / 150 - 170 °C / Autoclave 2.1: sodium amide / tetrahydrofuran / 1 h / 20 - 25 °C 2.2: 2 h / 30 - 45 °C 3.1: ethanol / 2.5 h / -2 - 0 °C View Scheme

maleic acid (110-16-7) + Chlorpheniramine (132-22-9) → chlorphenamine maleate (113-92-8)

Conditions	Yield
In ethanol at -2 - 0℃; for 2.5h;	350 g
With pyrographite In ethanol at 80℃; for 1.5h; Temperature; Large scale;
With pyrographite In ethanol at 80℃; for 2h; Temperature;

+ 2-(4-chlorobenzyl)pyridine + maleic acid (110-16-7) → chlorphenamine maleate

Conditions	Yield
Stage #1: 2-(4-chlorobenzyl)pyridine With sodium amide In toluene Reflux; Stage #2: 2-(N,N-dimethylamino)ethyl bromide In toluene for 6h; Reflux; Stage #3: maleic acid In toluene	24.1 g

→ chlorphenamine maleate (113-92-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: manganese; trifluoroacetic acid / acetonitrile / 0.17 h 1.2: 12 h / 30 - 40 °C 2.1: sodium amide / toluene / Reflux 2.2: 6 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: manganese; trifluoroacetic acid / acetonitrile / 0.17 h 1.2: 12 h / 30 - 40 °C 2.1: sodium amide / toluene / Reflux 2.2: 6 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: manganese; trifluoroacetic acid / acetonitrile / 0.17 h 1.2: 12 h / 30 - 40 °C 2.1: sodium amide / toluene / Reflux 2.2: 6 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: manganese; trifluoroacetic acid / acetonitrile / 0.17 h 1.2: 12 h / 30 - 40 °C 2.1: sodium amide / toluene / 0.33 h / 20 °C 2.2: 8 h / Reflux 3.1: water; N,N-dimethyl-formamide / 24 h / 100 °C 3.2: 2 h / 80 °C View Scheme

1-Chloro-4-(chloromethyl)benzene (104-83-6) → chlorphenamine maleate (113-92-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: manganese; trifluoroacetic acid / acetonitrile / 0.17 h 1.2: 12 h / 30 - 40 °C 2.1: sodium amide / toluene / Reflux 2.2: 6 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: manganese; trifluoroacetic acid / acetonitrile / 0.17 h 1.2: 12 h / 30 - 40 °C 2.1: sodium amide / toluene / 0.33 h / 20 °C 2.2: 8 h / Reflux 3.1: water; N,N-dimethyl-formamide / 24 h / 100 °C 3.2: 2 h / 80 °C View Scheme

4-(2-Pyridinylmethyl)phenylamine (58498-12-7) → chlorphenamine maleate (113-92-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium nitrite; hydrogenchloride / water / 0.33 h / 0 - 5 °C 1.2: 4 h / 20 °C 2.1: sodium amide / toluene / Reflux 2.2: 6 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: sodium nitrite; hydrogenchloride / water / 0.33 h / 0 - 5 °C 1.2: 4 h / 20 °C 2.1: sodium amide / toluene / 0.33 h / 20 °C 2.2: 8 h / Reflux 3.1: water; N,N-dimethyl-formamide / 24 h / 100 °C 3.2: 2 h / 80 °C View Scheme

2-(4-chlorobenzyl)pyridine (4350-41-8) → chlorphenamine maleate (113-92-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium amide / toluene / 0.33 h / 20 °C 1.2: 8 h / Reflux 2.1: water; N,N-dimethyl-formamide / 24 h / 100 °C 2.2: 2 h / 80 °C View Scheme

potassium pentacyanonitrosylchromate(III) monohydrate + chlorphenamine maleate (113-92-8) → {Cr(NO)(CN)2(chloropheniramine maleate)2(H2O)}

Conditions	Yield
With CH3COOH In acetic acid byproducts: CH3COOK, H2O, HCN; aq. acetic acid; 20-30 min, 80°C; CO2 bubbled (few h) to remove HCN; ppt. filtered, washed (H2O repeatedly; ethanol); dried (vac., over silica gel, room temp., to const. wt.); elem.anal.;	55%

cobalt(II) nitrate hexahydrate + salicylaldehyde anthranilic acid (122630-45-9, 150063-91-5, 7361-93-5) + chlorphenamine maleate (113-92-8) → Co(OC6H4CHNC6H4COO)(C5H4NCH(CH2CH2N(CH3)2)C6H4Cl)(H2O)*(HCCOOH)2 (151958-93-9)

Conditions	Yield
In ethanol byproducts: HNO3; refluxing ethanolic solns. of metal salt, schiff base and heterocyclic base in 1:1:1 molar ratio for 2-5 h, pptn.; filtn., washing with ethanol, drying in vacuo, elem. anal.;	53%

tetracyanodinitrosylmolybdate(0) + chlorphenamine maleate (113-92-8) → Mo(NO)2(CN)2(C5H4NCH(CH2CH2N(CH3)2)C6H4Cl)2*2(CHCOOH)2*2H2O=(Mo(NO)2(CN)2(C16H19N2Cl)2)*((CHCOOH)2)2*2H2O

Conditions	Yield
In water; acetic acid addn. of ligand in a mixt. of water/acetic acid to a filtered aq. soln. of molybdate with shaking, refluxing for 4-5 h over a hot plate at 80°C; filtn. by suction, washing several times with dilute acetic acid, finally with water, drying in vacuo at room temp. to a constant weight, elem. anal.;	52%

cobalt(II) nitrate hexahydrate + chlorphenamine maleate (113-92-8) + 2-(salicylideneamino)thiophenol (3449-05-6) → Co(OC6H4CHNC6H4S)(C5H4NCH(CH2CH2N(CH3)2)C6H4Cl)(H2O)*(HCCOOH)2 (151987-76-7)

Conditions	Yield
In ethanol byproducts: HNO3; refluxing ethanolic solns. of metal salt, schiff base and heterocyclic base in 1:1:1 molar ratio for 2-5 h, pptn.; filtn., washing with ethanol, drying in vacuo, elem. anal.;	50%

chlorphenamine maleate (113-92-8) → dextrochlorpheniramine maleate (2438-32-6) + (-)-Chlorpheniramine maleate (23095-76-3)

Conditions	Yield
With sodium dihydrogenphosphate; phosphoric acid In methanol; water pH=2.75; Reagent/catalyst; Ionic liquid; Resolution of racemate;
With maleic anhydride-β-cyclodextrin modified Fe3O4 Resolution of racemate; Optical yield = 13.7 %ee;
With tetramethylammonium hydroxyproline; clindamycin phosphate In methanol; water at 20℃; pH=7.6; pH-value; Solvent; Temperature; Resolution of racemate; enantioselective reaction;
With β‐cyclodextrin In aq. phosphate buffer pH=2.5; Resolution of racemate;

Eosin Y (548-26-5, 602-47-1, 17372-87-1) + chlorphenamine maleate (113-92-8) → 2C16H19ClN2*2C4H4O4*2Na(1+)*C20H6Br4O5(2-)

Conditions	Yield
In water at 23℃; for 0.166667h; pH=3.72; Solvent; pH-value; Temperature;

Upstream product

• 140-53-4 p-chlorobenzyl cyanide 
• 110-16-7 maleic acid 
• 132-22-9 Chlorpheniramine 
• 4350-41-8 2-(4-chlorobenzyl)pyridine 
• 64-18-6 formic acid 
• 20619-13-0 Didesmethylchlorpheniramine 
• 58498-12-7 4-(2-Pyridinylmethyl)phenylamine 
• 104-83-6 1-Chloro-4-(chloromethyl)benzene 
• 109-04-6 2-bromo-pyridine 
• 5459-68-7 2-(N,N-dimethylamino)ethyl bromide 
• 107-99-3 2-(dimethylamino)ethyl chloride 

Downstream Products

• 2438-32-6 dextrochlorpheniramine maleate 
• 23095-76-3 (-)-Chlorpheniramine maleate 

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Relevant articles and documents

Chlorpheniramine maleate crystal form preparation method

The invention discloses a chlorpheniramine maleate crystal form preparation method which is different from an existing crystal form preparation method, wherein two solvents are used in the crystallization process, the impurity content in a finished product is effectively reduced, the yield and the purity are improved, the crystal form is stable, the crystal form cannot be changed due to the change of the solvent proportion, and industrial production is facilitated.

1/10-water maleic acid chlorpheniramine compound and pharmaceutical composition thereof (by machine translation)

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Chlorpheniramine maleate salifying substance and synthesis method and application thereof

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The invention belongs to the field of organic synthesis of the drug, in particular to a new synthetic method of chlorpheniramine maleate. The invention comprises the following sequence of steps: (1) under acidic conditions, to [...] in cobalt catalyst, in the presence of a [...] and 2 - halo pyridine react, generating 2 - to the benzylic pyridine; (2) 2 - to the benzylic pyridine in under the action of the sodium amide and N, N - dimethyl base halogen ethane reaction, generating the cream, chlorpheniramine and maleic acid and get chlorpheniramine maleate. The method of reaction steps is relatively short, the raw material is cheap, the process is simple, easy to operate, does not need special reaction conditions, therefore is more suitable for industrial production. (by machine translation)

Novel synthetic method for chlorpheniramine maleate

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Pharmaceutical compositions are provided which contain hollow fine tube drug delivery systems. The compositions comprise a pharmaceutically suitable carrier, preferably in the form of a capsule, tablet, suspension, or suppository, and at least one drug delivery system which consists essentially of (1) a polymeric tube having a membrane outer sheath and a hollow core, and (2) at least one drug compound contained within the core, said system contained in the composition in an amount sufficient to deliver a therapeutic amount of the drug contained therein at a predetermined rate over a predetermined period of time. By varying the polymer, the permeability of the outer sheath, the drug, the drug concentration in the hollow core of the tube, the tube diameter, the tube length, the tube core diameter, and the sealing of the tube ends, a wide variety of drug therapeutic amounts, rates and dosing times can be achieved.

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