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

Originator

Actidil,Burroughs-Wellcome,US,1958

Uses

Antihistaminic.

Definition

ChEBI: An N-alkylpyrrolidine that is acrivastine in which the pyridine ring is lacking the propenoic acid substituent. It is a sedating antihistamine that is used (generally as the monohydrochloride monohydrate) for the relief of the symptoms o uticaria, rhinitis, and various pruritic skin disorders.

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.

Brand name

Actidil (GlaxoSmithKline); Myidyl (USl).

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 Simple and convenient synthesis of triprolidine

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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.