Ticlopidine hydrochloride

Ticlopidine hydrochloride is an adenosine diphosphate (ADP) receptor inhibitor against platelet aggregation with IC50 of ~2 μM.Target: Adenosine diphosphate (ADP)Ticlopidine (trade name Ticlid) is an antiplatelet drug in the thienopyridine family. Ticlopidine hydrochloride inhibits platelet aggregation with IC50 of ~2 μM in men. Like clopidogrel, it is an adenosine diphosphate (ADP) receptor inhibitor. It is used in patients in whom aspirin is not tolerated, or in whom dual antiplatelet

Ticlopidine Hydrochloride is the hydrochloride salt form of ticlopidine, a thienopyridine derivative with anticoagulant property. Ticlopidine hydrochloride irreversibly inhibits adenosine-diphosphate (ADP)-induced platelet-fibrinogen binding by binding to the glycoprotein (GP) IIb/IIIA complex, one of the two purinergic receptors activated by ADP. Inhibition of the receptor activation causes the inhibition of adenylyl cyclase, results in decreased levels of cyclic adenosine monophosphate and thereby interferes with platelet membrane function and subsequent, platelet-platelet interaction, release of platelet granule constituents and prolongation of bleeding time.|An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.

The preparation method of ticlopidine hydrochloride as shown in Fig. 2 comprises the following steps:1. p-toluenesulfonyl protection:In a 1000 ml reaction flask, 500 ml of toluene, 50 g of thiophene ethanol and 80 g of p-toluenesulfonyl chloride were charged and stirred to controlAt a temperature of 0 ° C, 47 g of triethylamine was added dropwise, dropping for about 30 min, and the temperature was raised to 25 ° C for 3 hours.Add 400ml of water, washed twice, washed with toluene layer directly to the next step reaction.2. Condensation reactionThe reaction solution of toluene in the previous step was added to a 1000 ml reaction flask, followed by the addition of 114 g of o-chlorobenzylamine and heating to 90° C for 3 hours. After the reaction, the mixture was cooled to 25 ° C and stirred for 1 hour. The filtrate was added with 200 ml of water, and hydrochloric acidAdjust the pH of the system to 8.5, stratify the upper layer of toluene and continue dropping hydrochloric acid to adjust the pH to 5, then cool the system to 2 ° CThe crystals were mixed for 4 hours and filtered, and the filter cake was dried in vacuo at 50 ° C to give 96 g of the condensate hydrochloride.3 • Closed loop reactionTo the 1000 ml reaction flask was added 96 g of the condensate hydrochloride, 400 ml of 1, 3-dioxane and 5 ml of hydrochloric acid, To 90 ° C for 6 hours. After the reaction, the mixture was cooled to 7 ° C and stirred for 3 hours. The filter cake was washed with a small amount of 1, 3-dioxetane After 50 ° C vacuum drying, 95 g of ticlopidine hydrochloride was obtained4 • RefinedIn a 1000 ml reaction flask, 95 g of crude ticlopidine hydrochloride and 500 ml of absolute ethanol were added and heated to 72 ° C with stirring, About 10 minutes after the solid is completely dissolved by adding 2g activated carbon, insulation bleaching 20 minutes after the hot filter, the filtrate gradually coolingThe crystals were crystallized at 4 ° C for 4 hours and filtered. The filter cake was washed with a small amount of absolute ethanol and dried in vacuo at 50 ° C to give 91 g of tithiol hydrochloridePrecision products. Total yield 82percent, purity 99.9percentIn a 1000 ml reaction flask was added 96 g of condensate hydrochloride, 400 ml of 1, 3-dioxolane and 5 ml of hydrochloric acid, the mixture was heated to 90 ° C with stirring for 6 hours, after completion of the reaction, the mixture was cooled to 7 ° C and stirred for 3 hours, filtered, the cake was washed with a small amount of 1, 3-dioxane and dried in vacuo at 50 ° C to give 95 g of crude ticlopidine hydrochloride.96 g of Condensate hydrochloride was added in a 1000 ml reaction flask, 400ml 1, 3-dioxane and 5 ml of hydrochloric acid were added, and stirred by heating to 90 ° C for 6 hours. After the reaction, the mixture was cooled to 7 ° C and stirred for 3 hours, filtered, filter cake was washed with a small amount of 1, 3-dioxane, after washing, the resultant was vacuum dried at 50 ° C to obtain crude 95 g ticlopidine hydrochloride.In a 500 ml three-necked flask, 12.7 g (0.1 mol) of 2-thiophenethylamine, 9 g (0.3 mol) of formaldehyde, 50 g of dichloromethane and 50 g of dichloroethane, S2O82- / SnO2-Fe2O3 solid super acid 12 grams, Turn on stirring, and heated to 60 ° C for 5 hours after the reaction was stopped heating, The reaction solution was then cooled to room temperature, 19.3 g (0.12 mol) of 2-chlorobenzyl chloride and 10.1 g of solid base-III were further added to the reaction mixture, Continue to heat and make it at 60 temperature for 1 hour, stop heating and stirring, Let stand, filtered to remove residue, the filtrate was passed into hydrogen chloride gas to give 26.1 g of triclopyridine hydrochloride, yield 87percent.In a 1000 ml reaction flask was added 96 g of condensate hydrochloride, 400 ml of 1, 3-dioxane and 5 ml of hydrochloric acid, The mixture was heated to 90 ° C with stirring for 6 hours, After completion of the reaction, the mixture was cooled to 7 ° C and stirred for 3 hours.filter, Filter cake with a small amountAfter washing 1, 3-dioxane and drying at 50 ° C, 95 g of crude ticlopidine hydrochloride was obtained.;_ 4. Refining;_ Was added in a 1000 ml reaction flask95g ticlopidine hydrochloride crude and500ml of anhydrous ethanol, heated to 72 ° C under stirring, After about 10 minutes, the solid is completely dissolved and added2g of activated carbon, Insulation 20 minutes after the hot decolorization filter, The filtrate gradually cooled to 4 ° C stirring crystallization 4 hours, filter, The filter cake was washed with a small amount of absolute ethanol and dried in vacuo at 50 ° C to give 91 g of ticlopidine hydrochloride. Total yield 82percent, purity 99.9percentd 8A.

mucolytic, antibacterial, surface active agent Ticlopidine hydrochloride is suitable for the prevention and treatment of circulatory disorders of the heart, brain and other arteries caused by high platelet aggregation, and the adjuvant treatment of percutaneous coronary intervention.

Molecular Weight:300.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:299.0302260
Monoisotopic Mass:299.0302260
Topological Polar Surface Area:31.5
Heavy Atom Count:18
Complexity:261
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes