Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate Chemical Properties

Melting point:

169-173°C

Boiling point:

704.5±70.0 °C(Predicted)

Density 

1.35±0.1 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,2-8°C

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid:particulate/powder

pka

4.15±0.10(Predicted)

Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate Usage And Synthesis

Chemical Properties

Off-White Solid

Uses

Candesartan Methyl Ester (Candesartan Cilexetil EP Impurity I) is an intermediate in the preparation of Candesartan (C175575).

Synthesis

1. Methyl 2-ethoxy-1-[(2'-cyanobiphenyl-4-yl)methyl]-1H-benzimidazole-7-carboxylate (310 g) and toluene (2.48 L) were added to a reactor, followed by tributyltin chloride (737 g), sodium azide (146 g) and tetrabutylammonium bromide (31 g). 2. The reaction mixture was slowly heated to 110 °C and maintained at 110-115 °C for 24 h, during which the progress of the reaction was monitored by TLC. 3. After completion of the reaction, the reaction mixture was cooled to 15 °C and methanol (3.1 L), water (2.17 L) and acetic acid (930 g) were added sequentially. 4. The mixture was stirred at 15-20 °C for 1 h to promote product separation. 5. After addition of toluene (1.24 L), the reaction mixture was filtered at 15-20 °C. 6. the filter cake was washed thoroughly with water (0.93 L) until the pH of the wash solution reached 5.5-7.0 to completely remove the acid. 7. The filter cake was washed again with toluene (0.62 L) and dried by suction filtration. 8. The product was air dried at 50-55 °C to give methyl 2-ethoxy-1-[[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]benzimidazole]-7-carboxylate. Yield: 290 g (85%).

IC 50

AT2 Receptor: 0.11 μM (IC₅₀)

References

[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
[2] Patent: WO2005/51929, 2005, A1. Location in patent: Page/Page column 18
[3] Patent: US2009/203920, 2009, A1. Location in patent: Page/Page column 4
[4] Patent: EP1420016, 2004, A1. Location in patent: Page 19
[5] Patent: WO2009/157001, 2009, A2. Location in patent: Page/Page column 3

Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate(139481-69-9)Related Product Information

• Candesartan cilexetil
• Trityl candesartan cilexetil
• Candesartan Methyl Ester Desethyl Analog
• N-Trityl Candesartan Ethyl Ester
• 5-(phenylazo)salicylic acid
• CV 15959
• CANDESARTAN-D5
• Candesartan
• Ethyl-2-Ethoxy-1-[[(2'-Cyanobiphenyl-4-yl) Methyl] Benzimidazole]-7-Carboxylate
• 2-[[(2'-Cyano[1,1'-biphenyl]-4-yl)methyl]amino]-3-nitro-benzoic acid ethyl ester
• BENZOIC ACID, 2-[[(1,1-DIMETHYLETHOXY)CARBONYL]AMINO]-3-NITRO-METHYL ESTER
• Methyl 2-ethoxybenzimidazole-7-carboxylate
• Ethyl -2-ethoxy-1-[[(2-(1Htetrazol-5-yl)biphenyl-4-yl-) methyl]
• BENZOIC ACID, 2-[[(2'-CYANO[1,1'-BIPHENYL]-4-YL)METHYL]AMINO]-3-NITRO-METHYL ESTER
• 2-[1.1-dimethyl ethyl ethoxy carbonyl]amino-3-nitro benzoic acid ethyl ester
• Ethyl-3-Amino-2-[(2'-Cyanoiphenyl-4-yl) Methyl]-Amino Benzoate
• CANDESARTAN CILEXETIL-D11
• O-Desetheyl Candesartan Ethyl Ester