Convergent Synthesis of Angiotensin II Receptor Blockers through C–H Arylation of 1-Benzyl-5-phenyl-1H-tetrazole with Functionalized Aryl Bromides

Abstract

Highly convergent synthesis of angiotensin II receptor blockers has been accomplished by means of late-stage C–H arylation using functionalized aryl bromides. C–H arylation of 1-benzyl-5-phenyl-1H-tetrazole with aryl bromides carrying methyl 2-ethoxybenzimidazole-7-carboxylate unexpectedly provided coupling products where ethyl group was migrated from oxygen to nitrogen atom. The O-to-N ethyl migration was completely suppressed by the use of N-pivaloyl-l-valine rather than the combined use of triphenylphosphine and sodium mesitylenesulfonate to result in the preferential formation of a key intermediate of candesartan cilexetil. In contrast, when an aryl bromide having ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate was employed, the C–H arylation proceeded smoothly to provide a late-stage intermediate, which rapidly led to olmesartan medoxomil in 3 steps.

Key words

tetrazole - ruthenium - hypertensive drugs

Publikationsverlauf

Eingereicht: 12. März 2021

Angenommen nach Revision: 31. März 2021

Accepted Manuscript online:
31. März 2021

Artikel online veröffentlicht:
14. April 2021

• References

• 1a Kubo K, Inada Y, Kohara Y, Sugiura Y, Ojima M, Itoh K, Furukawa Y, Nishikawa K, Naka T. J. Med. Chem. 1993; 36: 1772
• 1b Kubo K, Kohara Y, Imamiya E, Sugiura Y, Inada Y, Furukawa Y, Nishikawa K, Naka T. J. Med. Chem. 1993; 36: 2182
• 1c Kubo K, Kohara Y, Inada Y, Shibouta Y, Furukawa Y, Kato T, Nishikawa K, Naka T. J. Med. Chem. 1993; 36: 2343
• 2 Brousil JA, Burke JM. Clin. Ther. 2003; 25: 1041
• 3a Seki M. ACS Catal. 2011; 1: 607
• 3b Seki M, Nagahama M. J. Org. Chem. 2011; 76: 10198
• 3c Seki M. Synthesis 2012; 44: 3231
• 3d Seki M. RSC Adv. 2014; 4: 29131
• 3e Seki M. Synthesis 2014; 46: 3249
• 3f Seki M. ACS Catal. 2014; 4: 4047
• 3g Seki M. Arylation Using a Ruthenium(II) Catalyst. In Science of Synthesis, Catalytic Transformation via C–H Activation, Vol. 1, Chap. 1.1.4. Yu J.-Q. Thieme Verlag; Stuttgart: 2015: 119-154
• 3h Seki M. Synthesis 2015; 47: 1423
• 3i Seki M. Synthesis 2015; 47: 2985
• 3j Seki M. Org. Process Res. Dev. 2016; 20: 867
• 4 Hubrich J, Ackermann L. Eur. J. Org. Chem. 2016; 3700
• 5 Yeung CS, Hsieh TH. H, Dong VM. Chem. Sci. 2011; 2: 544
• 6 Ackermann L, Lygin AV. Org. Lett. 2011; 13: 3332