486-12-4

Basic information

• Product Name: Triprolidine
• Synonyms: (e)-2-(1-(4-methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl)pyridine;(E)-2-[3-(1-Pyrrolidinyl)-1-p-toluenepropenyl]pyridine;(e)-pyridin;2-[(1Z)-1-(4-Methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl]pyridine;2-[1-(4-methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl]pyridine;NCI-C61450;Pyridine, 2-[1-(4-methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl]-, (E)-;Pyridine, 2-[3-(1-pyrrolidinyl)-1-p-tolylpropenyl]-, (E)-
• CAS NO: 486-12-4
• Molecular Formula: C₁₉H₂₂N₂
• Molecular Weight: 278.39
• EINECS: 207-627-0
• Mol File: 486-12-4.mol
• Article Data: 4

Chemical Properties

• Melting Point: 59-61°
• Boiling Point: 435.4 °C at 760 mmHg
• Flash Point: 217.1 °C
• Appearance: crystals
• Density: 1.061 g/cm³
• Vapor Pressure: 6.16E-09mmHg at 25°C
• PKA: pKa 4.01(H2O t = 23.0) (Uncertain);9.69(H2O t = 23.0) (Uncertain)
• CAS DataBase Reference: Triprolidine(CAS DataBase Reference)
• NIST Chemistry Reference: Triprolidine(486-12-4)
• EPA Substance Registry System: Triprolidine(486-12-4)

Safety Data

• Hazardous Substances Data: 486-12-4(Hazardous Substances Data)

Usage

Description

Triprolidine is an N-alkylpyrrolidine antihistamine, specifically acrivastine without the propenoic acid substituent on the pyridine ring. It is characterized by its sedating properties and is commonly used to alleviate symptoms of various conditions.

Uses

Used in Pharmaceutical Industry:
Triprolidine is used as an antihistaminic agent for the relief of symptoms associated with urticaria, rhinitis, and various pruritic skin disorders. Its sedating nature makes it an effective treatment for these conditions.
Brand names:
Actidil (GlaxoSmithKline)
Myidyl (USL)

Originator

Actidil,Burroughs-Wellcome,US,1958

Manufacturing Process

4-Methylacetophenone is first reacted with paraformaldehyde and then with pyrrolidine to give p-methyl-ω-pyrralidinopropiophenone. Atomized lithium (26 g, 3.75 mols) and sodium-dried ether (200 cc) are placed in a 3-liter, 3-necked flask fitted with a Herschberg stirrer, thermometer pocket and a water condenser closed by a calcium chloride tube. A slow stream of dry nitrogen is blown through the flask, which is cooled to - 10°C and n-butyl chloride (138 g, 156 cc, 1.5 mols) is run in with rapid stirring; the mixture is stirred for a further 30 minutes, and then cooled to - 60°C 2-Bromopyridine (193 g, 1.22 mols) is then added dropwise over 20 minutes, the temperature of the reaction mixture being maintained at -50°C. The mixture is stirred for 10 minutes at -50°C and p-methyl-ω- pyrrolidinopropiophenone (112.5 g, 0.5 mol) in dry benzene is then added dropwise over ca 30 minutes, at a temperature of -50°C. The mixture is stirred for a further 2 hours, the temperature being allowed to rise to -30°C but no higher. The mixture is poured onto excess ice, acidified with concentrated hydrochloric acid, the ether layer separated and extracted with water (1 x 200 cc). The combined aqueous extracts are washed with ether (1 x 200 cc) basified with 0.880 ammonia and extracted with chloroform (3 x 350 cc); the extract is washed with water (2 x 100 cc), dried over sodium sulfate, evaporated, and the residue extracted with boiling light petroleum (BP 60° to 80°C; 10 volumes), filtered hot and evaporated to dryness. The residue is recrystallized from alcohol to give a cream solid (119 g, 80%), MP 117° to 118°C. Recrystallization gives 1-(4-methylphenyl)-1-(2-pyridyl)-3- pyrrolidonopropan-1-ol, MP 119° to 120°C. 1-(4-Methylphenyl)-1-(2-pyridyl)-3-pyrrolidinopropan-1-ol (10.0 g) is heated in a steam bath for 30 minutes with 85% aqueous sulfuric acid (30 cc). The solution is then poured onto crushed ice, excess of ammonia solution added and the liberated oil extracted with light petroleum (BP 60° to 80°C). The extract is dried over anhydrous sodium sulfate and the solvent evaporated to leave an amber syrup (8.8 g) consisting of the cis and trans isomers of 1-(4- methylphenyl)-1-(2-pyridyl)-3-pyrrolidinoprop-1-ene as described in US Patent 2,712,023. The isomers may be separated by base exchange chromatography. The 4-methyl-ω-pyrrolidinopropiophenone required as the starting product for the preparation of the carbinol is prepared by the Mannich reaction (Blicke, Organic Reactions, 1942, vol 1, p 303; Adamson & Billinghurst, Journal of the Chemical Society, 1950,1039) from 4-methylacetophenone and pyrrolidine. The hydrochloride has a MP of 170°C with decomposition.

Therapeutic Function

Antihistaminic

InChI:InChI=1/C19H22N2.ClH/c1-16-7-9-17(10-8-16)18(19-6-2-3-12-20-19)11-15-21-13-4-5-14-21;/h2-3,6-12H,4-5,13-15H2,1H3;1H/b18-11+;

Upstream product

• 78539-88-5 2-(4-toluoyl)pyridine 
• 70708-28-0 1-[2]pyridyl-3-pyrrolidino-1-p-tolyl-propan-1-ol 

Downstream Products

• 550-70-9 Pro-Actidil 

Relevant articles and documents

A PROCESS FOR PREPARATION OF E-ISOMER OF 1-(4-METHYLPHENYL)- 1-(2-PYRID YL)-3-PYRROLIDINO PROP-1-ENE AND ACID ADDITION SALTS THEREOF

A process for preparation of E-isomer of 1-(4-methylphenyl)-1-(2-pyridyl)-3- pyrrolidinoprop-1-ene of Formula-I, and acid addition salts thereof, said process comprising; dehydrating 1-(4-methylphenyl)-l -(2-pyridyl)-3-pyrrolidinopropan-1-ol of Formula III followed by adding a base solution to obtain a mixture of E and Z isomers of 1-(4-methylphenyl)-1-(2-pyridyl)-3-pyrrolidinoprop-1-ene, and washing said mixture of E and Z isomers of 1-(4-methylphenyl)-1-(2-pyridyl)-3- pyrrolidinoprop-1-ene with water to dissolve Z isomer and to obtain E-isomer of 1- (4-methylphenyl)-1-(2-pyridyl)-3-pyrrolidinoprop-1-ene of Formula I, which is substantially free from Z isomer.

A PROCESS FOR THE SYNTHESIS OF (E) -2-[1 - (4 - METHYL PHENYL) -3-(1-PYRRONYL)-1 - PROPENYL] PYRIDINE (TRIPROLIDINE)

A Process for the synthesis of (E) - 2 - [1 - (4 - methyl phenyl) -3- (1- pyrrolidinyl)-l- propenyl] pyridine (TRIPROLIDINE) by reacting 2-(l-pyrrolidino)ethyl triphenyl phosphonium bromide with 2-(p-toluoyl) pyridine in presence of aprotic solvent and a base, isomeising in presence of acid catalyst.