(Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate

Chemical Properties

White Solid

Uses

Azilsartan (A926900) derivative. Intermediate in the synthesis of angiotensin II receptor antagonist.

Synthesis

N,N-dimethylacetamide (2 L) and water (16 L) were added to the reaction flask, followed by hydroxylamine hydrochloride (3.37 kg, 48.6 mol) and sodium carbonate (5.15 kg, 48.6 mol). Methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate (2 kg, 4.86 mol) was added to the reaction mixture and the reaction was carried out at 70 °C for 18 hours. After completion of the reaction, it was cooled to room temperature and water (2 L) was added to promote precipitation of the product. The precipitate was collected by filtration to afford methyl 2-ethoxy-1-[2'-(N'-hydroxyformamidino)biphenyl-4-yl]-1H-benzimidazole-7-carboxylate (1.94 kg, 37.70 mol). The product was analyzed by HPLC (refer to Example 1 conditions) with 98.9% purity and 90% yield.

References

[1] Patent: CN103408500, 2016, B. Location in patent: Paragraph 0026; 0046-0047
[2] Patent: WO2013/114305, 2013, A1. Location in patent: Page/Page column 15; 16
[3] Organic Process Research and Development, 2015, vol. 19, # 4, p. 514 - 519
[4] Organic Process Research and Development, 2013, vol. 17, # 1, p. 77 - 86
[5] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 4, p. 929 - 936