1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester Chemical Properties

Melting point:

171-175°C

Density 

1.34±0.1 g/cm3 (20 ºC 760 Torr)

storage temp. 

Sealed in dry,Room Temperature

solubility 

DMSO (Slightly), Methanol (Slightly)

pka

6.99±0.20(Predicted)

form 

Solid

color 

White to Light Yellow

1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester Usage And Synthesis

Uses

Ethyl 2-?Ethoxy-?1-?((2''-?(5-?oxo-?2,?5-?dihydro-?1,?2,?4-?oxadiazol-?3-?yl)?-?[1,?1''-?biphenyl]?-?4-?yl)?methyl)?-?1H-?benzo[d]?imidazole-?7-?carboxylate is an impurity of Azilsartan (A926900), which is an analgesic and anti-inflammatory drug containing angiotensin II antagonists.

Synthesis

The synthesis of 1-[[2'-(2'-(N'-hydroxyformamidinyl)-[1,1'-biphenyl]-4-yl]methyl]-1H-benzo[d]imidazole-7-carboxylic acid ethyl ester and diethyl carbonate was carried out using ethyl 2-ethoxime (II) and diethyl carbonate as the raw materials for the synthesis of 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]-2-ethoxime (II) The general procedure for ethyl -7-carboxylate was as follows: ethoxime (II) (390 g, 851 mmol) was suspended in 3600 mL of diethyl carbonate. The suspension was heated to 65°C. An ethanolic solution of sodium ethoxide (21%, 400 mL, 1072 mmol) was added dropwise to the reaction mixture over 30 minutes at 65°C. After the dropwise addition, the reaction mixture was continued to be stirred at 65 °C for 30 min. Subsequently, the reaction mixture was cooled to 60 °C and water (1350 mL) was added. The resulting emulsion was stirred for at least 15 minutes. After separation of the layers, the organic phase was extracted with water (1350 mL). The aqueous phase extracts were combined, diluted with ethanol (1350 mL) and the temperature was adjusted to 40 °C. Acetic acid (111 mL, 1940 mmol) was added dropwise to the solution over 40 minutes at 40°C. The regenerated suspension was stirred at 40 °C for 30 min and then cooled to 20 °C. The solid product was separated by suction filtration and washed with water (2 x 450 mL). Finally, the product was dried in a vacuum desiccator at 45 °C to give 397 g of azilsartan ethyl ester (III) in 86% yield of the theoretical amount and 95.8% HPLC purity.

References

[1] Patent: WO2016/58563, 2016, A1. Location in patent: Page/Page column 7
[2] Patent: WO2012/139536, 2012, A1. Location in patent: Page/Page column 21

1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester(1403474-70-3)Related Product Information

• Azilsartan
• ethyl2-oxo-3-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)Methyl)-2,3-dihydro-1H-benzo[d]iMidazole-4-carboxylate
• 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, Methyl ester
• Azilsartan Impurity
• 1-[(2'-carbaMoylbiphenyl-4-yl) Methyl]-2-ethoxybenziMidazole-7-carboxylic acid
• (Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate
• 1-((2'-cyanobiphenyl-4-yl)Methyl)-2-ethoxy-1H-benziMidazole-7-carboxylic acid
• Azilsartan Impurity
• Olodaterol
• Methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate
• O-Desethyl Azilsartan
• Ethyl-3-Amino-2-[(2'-Cyanoiphenyl-4-yl) Methyl]-Amino Benzoate
• Azilsartan Impurity
• (Z)-2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d]iMidazole-4-carboxylic acid
• Azilsartan Impurity
• (Z)-Methyl 3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-2-oxo-2,3-dihydro-1H-benzo[d]iMidazole-4-carboxylate
• 1-[[2'-(AMinoiMinoMethyl)[1,1'-biphenyl]-4-yl]Methyl]-2-ethoxy-1H-benziMidazole-7-carboxylic Acid
• Azilsartan iMpurity I