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| | Triprolidine 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: | 486-12-4 | | MF: | C19H22N2 | | MW: | 278.39 | | EINECS: | 207-627-0 | | Product Categories: | | | Mol File: | 486-12-4.mol |  |
| | Triprolidine Chemical Properties |
| | 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 Preparation Products And Raw materials |
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