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| | Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate Basic information |
| | 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 Preparation Products And Raw materials |
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