486-12-4 Usage
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
Check Digit Verification of cas no
The CAS Registry Mumber 486-12-4 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 4,8 and 6 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 486-12:
(5*4)+(4*8)+(3*6)+(2*1)+(1*2)=74
74 % 10 = 4
So 486-12-4 is a valid CAS Registry Number.
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+;
486-12-4Relevant 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
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Page/Page column 5; 9-10, (2009/08/14)
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)
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Page/Page column 6, (2008/06/13)
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.
Use of a compound in providing refreshedness on waking and a method for the treatment of drowsiness therewith
-
, (2008/06/13)
There is disclosed the use of triprolidine for enabling an individual to wake refreshed after sleep and the method of treating such an individual with triprolidine. The triprolidine is administered shortly before a person wishes to fall asleep, preferably orally and most commonly in the form of a tablet containing less than 5 mg, eg 0.1 mg, 1.25 mg or 2.5 mg, of the active ingredient. The triprolidine is also effective in enabling an individual to sleep more easily.
