Category: 139481-72-4

Electric Literature of 139481-72-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 139481-72-4 name is Trityl candesartan, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Example 15: Deprotection without Acid; A solution of trityl candesartan c (TCS, 350 g, 410.3 mmol), toluene (1050 mL), methanol (2100 mL) and water (17.0 mL) was refluxed for about 2-4 h (HPLC control), the solvents were evaporated at 40-50 C/P<100 mbar to give a residue as a viscous oil, the residue was dissolved at 45-55 C in a mixture of Toluene/Methanol (1041g, 95: 5, w/w) to give a clear solution. The solution was cooled to (-5)- (20) C the solution was kept at this temperature for about 8-12 hr, the precipitated solids were filtered off, washed on the filter with cold Toluene (350 mL) to give a wet solid (295.8 g, 83.0%) 110 g of the wet solid were dried at 50C/10 mbar for 2-6 hr to give a wet white solid (94g (LOD= 15-25%) ). The wet white solid (43.75 g) was dissolved at 40-60 C in Ethanol Absolute (215-363 mL 6- 10V), the solution was filtered and returned to the reactor, then the solution was cooled to (-15)- (5) C and was kept at this temperature for about 2-24 hr. The precipitated solids were filtered off, washed with cold Ethanol Absolute (23-35 mL) to give wet solid which was dried at 50 C/10 mbar to constant weight to give cilexetil candesartan (21.5 g, 67 %). At the same time, in my other blogs, there are other synthetic methods of this type of compound, Trityl candesartan, and friends who are interested can also refer to it. Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/37821; (2005); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 139481-72-4, name is Trityl candesartan, molecular formula is C43H34N6O3, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 139481-72-4

Step I: Preparation of N-trityl candesartan cilexetilA mixture of N-trityl candesartan (Form A: 120 gm), potassium carbonate (48.58 gm), cilexetil chloride (54.48 gm) and dimethyl formamide (180 mL) at ambient temperature was heated to 60 C to 65 C followed by stirring at the same temperature for 2 hours and 30 minutes. The reaction mixture was cooled to 25 C to 30 C followed by addition of dichloromethane (600 mL) and ice cooled de-ionized water (1200 mL) at 10 C to 15 C to the reaction mass. The reaction was further stirred at 15 C to 20 C for 30 minutes followed by extraction of the aqueous layer with dichloromethane (120 mL) at 15 C to 30 C and washing with de-ionized water (2×600 mL) at ambient temperature.The organic layer was concentrated completely under vacuum at 30 C to 35 C followed by removal of traces of dichloromethane with cyclohexane (120 mL) and the further addition of cyclohexane (360 mL) to the residue at the ambient temperature. The reaction mixture was stirred at the same temperature for 14 hours followed by filtration and washing of the solid with cyclohexane (120 mL) which was suck dried under vacuum for 1 hour. Dichloromethane was again added (360 mL) at ambient temperature to the isolated solid followed by heating and stirring of the reaction mass at 30 C to 35 C for 30 minutes. The organic layer was concentrated under vacuum at 30 C to 35 C, cyclohexane (300 mL) added and the reaction mass was stirred further for 5 hours at the same temperature. The solid was filtered, washed with cyclohexane (120 mL) and suck dried under vacuum for 1 hour followed by further drying under vacuum for 16 hours at 35 C to 40 C.Chromatographic purity: 98.8%N-trityl desethylcandesartan cilexetil- 0.28%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 139481-72-4, its application will become more common.

Reference:
Patent; RANBAXY LABORATORIES LIMITED; SANJEEVI, Lakshmipathi V.; ALLADA, Suresh; KUMAR, Ashok; SINGH, Kaptan; GUNTU, Srinivasa Rao; WO2011/92666; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common heterocyclic compound, 139481-72-4, name is Trityl candesartan, molecular formula is C43H34N6O3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 139481-72-4.

Example 2: Method of Making Cilexetil Trityl Candesartan with a PTC; A suspension of trityl candesartan (2.0 g, 2.93 mmol), cilexetil chloride (1.21 g, 5.86 mmol), potassium carbonate (1.22 g, 8.83 mmol), and tetrabutylammoniumhydrogensulfate (0.2 g) in toluene (20 ml) was stirred at 50C to 55 C for about 8. 5 h. The reaction progress was monitored by TLC. The mixture was poured into water (100 ml) and neutralized with citric acid (solid). The organic layer was separated, washed with water, and extracted with ethyl acetate (20 ml x 3). The combined organic layers were washed with brine (10 ml), dried over sodium sulfate, and evaporated. The residue was triturated with hexane (20 ml) at 20-25C for about 30 min, filtered and dried at 40C and at less than about 30mbar to give white powder (1.68 gr, 67.2%), with 97.90% purity by HPLC.

The synthetic route of Trityl candesartan has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/37821; (2005); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 139481-72-4, name is Trityl candesartan belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. 139481-72-4

Potassium carbonate (60 gm), 1-chloroethylcyclohexyl carbonate (60 gm) and potassium iodide (20 gm) were added to the solution of 2-Ethoxy-1-[[2′-(N- triphenylmethyltetrazole-5-yl)biphenyl)-4-yl]methyl]benzimidazole-7-carboxylic acid (100 gm) in dimethylformamide (500 ml) at room temperature. Raised the temperature to 750C, stirred for 2 hours, cooled to room temperature and 5% sodium chloride solution (2000 ml) was added. Maintained for 15 minutes, ethyl acetate (400 ml) was added, stirred and separated the layers. Aqueous layer was extracted with ethyl acetate (400 ml), organic layer was taken, washed with 10% sodium chloride solution (400 ml), concentrated, and co-distilled with ethyl acetate (100 ml). Mixture of ethyl acetate (500 ml) and n-hexane (500 ml) were added to the residual mass, stirred for 6 hours at room temperature, cooled to 50C, stirred for 1 hour, filtered, then washed with mixture of ethyl acetate (50 ml) and n-hexane (200 ml) and dried for 6 hours to obtain 1-(Cyclohexyloxy carbonyloxy)ethyl-2-ethoxy-1-[[2′-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl] benzimidazole-7-carboxylate (110 gm, HPLC Purity: 99%).

The synthetic route of 139481-72-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; HETERO RESEARCH FOUNDATION; WO2009/157001; (2009); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem