91-81-6

Basic information

• Product Name: Tripelennamine
• Synonyms: Tripelennamine;1,2-Ethanediamine, N,N-dimethyl-N-(phenylmethyl)-N-2-pyridinyl-;PYRIBENZAMINE;Benzoxale;N,N-Dimethyl-N'-(phenylmethyl)-N'-(2-pyridinyl)-1,2-ethanediamine;Resistamine;Tonaril;Tripelenamine
• CAS NO: 91-81-6
• Molecular Formula: C₁₆H₂₁N₃
• Molecular Weight: 255.40
• EINECS: 202-100-1
• Mol File: 91-81-6.mol
• Article Data: 4

Chemical Properties

• Melting Point: 25°C
• Boiling Point: bp0.1 138-142°; bp1.7 185-190°; bp20 193-205°
• Appearance: oily liquid
• Density: 1.0683 (rough estimate)
• Refractive Index: nD25 1.5759-1.5765
• PKA: pKa 3.90±0.08(H2O t undefined I = 0.30 (NaCl)) (Uncertain);8.68±0.06(H2O t undefined I = 0.30 (NaCl)) (Uncertain)
• Water Solubility: 587.3mg/L(30 oC)
• Stability: Stable. Incompatible with strong oxidizing agents.
• CAS DataBase Reference: Tripelennamine(CAS DataBase Reference)
• NIST Chemistry Reference: Tripelennamine(91-81-6)
• EPA Substance Registry System: Tripelennamine(91-81-6)

Safety Data

• Hazardous Substances Data: 91-81-6(Hazardous Substances Data)

Usage

Chemical Properties

White, bitter, crystalline powder. Solutions are acid to litmus.Soluble in water and alcohol; very slightly soluble in ether; practically insoluble in chloroform and benzene; 1% solution in water has a pH of 4.3.

Originator

Pyribenzamine,Ciba,US,1946

Uses

Different sources of media describe the Uses of 91-81-6 differently. You can refer to the following data:
1. Medicine (antihistamine, sunburn treatment).
2. This drug lessens the allergic response of the organism caused by histamine. Tripelennamine is used for allergic symptoms, rhinitis, conjunctivitis, and for allergic and anaphylactic reactions. Synonyms of this drug are pelanin and pyribenzamine.

Manufacturing Process

46 g of α-benzylaminopyridine in 50 cc of dry toluene are heated to 80°C [the α-benzylaminopyridine may be obtained either according to the method of Tchitchibabine and Knunjanz, Berichte, 64, 2839 (1931), which consists in warming α-aminopyridine with benzaldehyde in formic acid, or alternatively by the action of benzyl chloride on sodio-α-aminopyridine]. To the toluene solution there are added gradually 9.5 g of 85% sodamide. After evolution of ammonia, the major part of the toluene is distilled off; into the pasty mass which remains there are poured 120 cc of an ethereal solution of 27 g of dimethylaminochloroethane. The mixture is heated until the temperature reaches 140°C, the ether distilling out, then finally heated under reduced pressure (150 mm Hg) for 1/2 hour. The mass is taken up with dilute hydrochloric acid and ether, neutralized at pH 7, and α-benzylaminopyridine separates. After making alkaline, using excess of potash, it is extracted with benzene, dried and distilled. The product thereby obtained, dimethylamino-ethyl-N-benzyl-N-α-arninopyridine, boils at 135° to 190°C/1.7 mm, according to US Patent 2,502,151.

Therapeutic Function

Antihistaminic

Reactivity Profile

Tripelennamine neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.

Health Hazard

SYMPTOMS: Symptoms of exposure to Tripelennamine may include euphoria, aplastic anemia, excitement, hallucinations, ataxia, incoordination, athetosis, convulsions, postictal depression, dry mouth, fixed dilated pupils, flushing of the face, fever, central nervous system depression, drowsiness and coma.

Fire Hazard

Flash point data for Tripelennamine are not available. Tripelennamine is probably combustible.

Safety Profile

Poison by ingestion and intraperitoneal routes. Human mutation data reported. Has been implicated in aplastic anemia. Used as an antdustasnine. Addicts have added it to paregoric to make "blue velvet," whtch can cause euphoria by injection. When heated to decomposition it emits toxic fumes of NOx.

Synthesis

Tripelennamine, N-benzyl-N′,N′-dimethyl-N-2-pyridylethylenediamine (16.1.6), is synthesized by reacting 2-benzylaminopyrridine (16.1.5) with 2-dimethylaminoethylchloride in the presence of sodium amide. 2-Benzylaminopyrridine, in turn, can be easily synthesized by reduction of a Schiff base, synthesized by condensation of 2-aminopyrridine with benzaldehyde.

Metabolic pathway

When pyribenzamine is incubated with rat liver microsomes, it is metabolized via N-oxide formation and N-dealkylation which includes removal of the dimethylamino moiety, the thiophenylmethyl moiety of methaphenilene, and the benzyl moiety of pyribenzamine.

InChI:InChI=1S/C16H21N3/c1-18(2)12-13-19(16-10-6-7-11-17-16)14-15-8-4-3-5-9-15/h3-11H,12-14H2,1-2H3

Synthetic route

2-(N-benzyl-pyridin-2-yl-amino)ethanol (872298-31-2) + dimethyl amine (124-40-3) → tripelennamine (91-81-6)

Conditions	Yield
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; bis[2-(diphenylphosphino)phenyl] ether In toluene at 20℃; Inert atmosphere; Reflux;	75%

pyridin-2-yl N,N,N',N'-tetramethyldiamidophosphate (874493-33-1) + N,N-dimethyl-N'-benzyl-1,2-ethanediamine (103-55-9) → tripelennamine (91-81-6)

Conditions	Yield
With TurboGrignard In tetrahydrofuran at 0 - 25℃; for 8h; Inert atmosphere;	74%

N-benzyl-N-(2-(dimethylamino)ethyl)pyridine-2-sulfonamide → tripelennamine (91-81-6)

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0); triphenylborane; sodium t-butanolate; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride In 5,5-dimethyl-1,3-cyclohexadiene at 60℃; for 16h; Glovebox; Inert atmosphere; Sealed tube;	49%

2-chloropyridine (109-09-1) → tripelennamine (91-81-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 12 h / 140 °C / Inert atmosphere; Sealed tube 2.1: lithium amide / acetonitrile / 0.08 h / Inert atmosphere 2.2: 8 h / Inert atmosphere; Reflux View Scheme

N,N-dimethyl-N'-(pyridine-2-yl)ethane-1,2-diamine (23826-72-4) + benzyl halide → tripelennamine (91-81-6)

Conditions	Yield
Stage #1: N,N-dimethyl-N'-(pyridine-2-yl)ethane-1,2-diamine With lithium amide In acetonitrile for 0.0833333h; Inert atmosphere; Stage #2: benzyl halide In acetonitrile for 8h; Inert atmosphere; Reflux;

2-hydroxypyridin (142-08-5) → tripelennamine (91-81-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: dmap; triethylamine / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 2: TurboGrignard / tetrahydrofuran / 8 h / 0 - 25 °C / Inert atmosphere View Scheme

tripelennamine (91-81-6) + 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester (21085-72-3) → [2-(Benzyl-pyridin-2-yl-amino)-ethyl]-((2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-dimethyl-ammonium; chloride (83708-12-7)

Conditions	Yield
With XAD-2 ion-exchange resin; sodium hydrogencarbonate In chloroform; water for 120h; Ambient temperature;	16%

tripelennamine (91-81-6) + ethyl bromoacetate (105-36-2) → ethoxycarbonylmethyl-[2-(benzyl-[2]pyridyl-amino)-ethyl]-dimethyl-ammonium; bromide

Conditions	Yield
With acetone

tripelennamine (91-81-6) → N'-benzyl-N,N-dimethyl-N'-[2]pyridyl-ethylenediamine-N-oxide (60317-19-3)

Conditions	Yield
With ethanol; dihydrogen peroxide

tripelennamine (91-81-6) → N-Benzyl-N'-methyl-N-pyridin-2-yl-ethane-1,2-diamine

Conditions	Yield
With oxygen; palladium on activated charcoal In methanol for 24h; Ambient temperature;

tripelennamine (91-81-6) + cucurbit[7]uril → tripelennamine-cucurbit[7]uril 1:1 complex

Conditions	Yield
In water pH=12; pH-value;

Upstream product

• 872298-31-2 2-(N-benzyl-pyridin-2-yl-amino)ethanol 
• 124-40-3 dimethyl amine 
• 109-09-1 2-chloropyridine 
• 23826-72-4 N,N-dimethyl-N'-(pyridine-2-yl)ethane-1,2-diamine 
• 142-08-5 2-hydroxypyridin 
• 874493-33-1 pyridin-2-yl N,N,N',N'-tetramethyldiamidophosphate 
• 103-55-9 N,N-dimethyl-N'-benzyl-1,2-ethanediamine 

Downstream Products

• 60317-19-3 N'-benzyl-N,N-dimethyl-N'-[2]pyridyl-ethylenediamine-N-oxide 
• 83708-12-7 [2-(Benzyl-pyridin-2-yl-amino)-ethyl]-((2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-dimethyl-ammonium; chloride 

Relevant articles and documents

Nickel-Catalyzed Intramolecular Desulfitative C - N Coupling: A Synthesis of Aromatic Amines

A nickel-catalyzed intramolecular C - N coupling reaction via SO2 extrusion is presented. The use of a catalytic amount of BPh3 allows the transformation to take place under much milder conditions (60 °C) than previously reported C - N coupling reactions by CO or CO2 extrusion (160-180 °C). In addition, this method displays good functional group tolerance and versatility, as it can be applied to the synthesis of dialkyl aryl amines, alkyl diaryl amines, and triaryl amines. The robustness of the desulfitative C - N coupling is demonstrated by three high-yielding gram-scale reactions.

Design, synthesis, and biological evaluation of novel FAK scaffold inhibitors targeting the FAK-VEGFR3 protein-protein interaction

Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor 3 (VEGFR3) are tyrosine kinases, which function as key modulators of survival and metastasis signals in cancer cells. Previously, we reported that small molecule chlorpyramine hydrochloride (C4) specifically targets the interaction between FAK and VEGFR3 and exhibits anti-tumor efficacy. In this study, we designed and synthesized a series of 1 (C4) analogs on the basis of structure activity relationship and molecular modeling. The resulting new compounds were evaluated for their binding to the FAT domain of FAK and anti-cancer activity. Amongst all tested analogs, compound 29 augmented anti-proliferative activity in multiple cancer cell lines with stronger binding to the FAT domain of FAK and disrupted the FAK-VEGFR3 interaction. In conclusion, we hope that this work will contribute to further studies of more potent and selective FAK-VEGFR3 protein-protein interaction inhibitors.