Triprolidine Property

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

Hazardous Substances Data

486-12-4(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

Triprolidine Chemical Properties,Usage,Production

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