Triprolidine Chemical Properties

Melting point:

59-61°

Boiling point:

435.4±34.0 °C(Predicted)

Density 

1.061±0.06 g/cm3(Predicted)

pka

pKa 4.01(H2O t = 23.0) (Uncertain);9.69(H2O t = 23.0) (Uncertain)

CAS DataBase Reference

486-12-4(CAS DataBase Reference)

NIST Chemistry Reference

Triprolidine(486-12-4)

Safety Information

Hazardous Substances Data

486-12-4(Hazardous Substances Data)

Triprolidine Usage And Synthesis

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

Triprolidine(486-12-4)Related Product Information

• Povidone iodine
• N-Methyl-2-pyrrolidone
• DIPHENYLCYCLOPROPENONE
• Pyridine
• Polyvinylpyrrolidone
• 1-Hexadecylpyridinium bromide
• Cetylpyridinium chloride
• 1-Phenyl-2-nitropropene
• Triprolidine hydrochloride,TRIPROLIDINE HYDROCHLORIDE MONOHYDRATE,TRIPROLIDINE HCL USP,TRIPROLIDINE HCL MONOHYDRATE
• METHYL-2-PYRROLIDONE
• 2-Benzylpyridine
• ALPHA,P-DIMETHYLSTYRENE
• Acrivastine
• 2-Vinylpyridine
• TRANS-TRIPROLIDINE HYDROCHLORIDE,TRIPROLIDINE HCL
• Triprolidine
• N,N-DIETHYLALLYLAMINE
• (ParaMethylAcetophenone)Triprolidine