1-(1-((2′-(1H-Tetrazol-5-yl)biphenyl-4-yl)methyl)-4-(2-hydroxy propan-2-yl)-2-propyl-1H-imidazol-5-yl)-3-methylbutan-1-one

Preparation of 1-(1-((2′-(1H-Tetrazol-5-yl)biphenyl-4-yl)methyl)-4-(2-hydroxy propan-2-yl)-2-propyl-1H-imidazol-5-yl)-3-methylbutan-1-one (12)

Formic acid (50 mL) was added to a solution of 13 (10.0 g, 0.0137 mole) in methanol-acetonitrile (1 : 1, 150 mL) and heated to 50°C for 4 hours. The solution was cooled to room temperature, and the solvents were removed under reduced pressure. The residue was taken in water (100 mL) and extracted with ethyl acetate ( × 2 5 0 mL). The combined organic extracts were washed with 15% NaHCO3 solution (50 mL) and dried over anhydrous sodium sulfate. Evaporation of the solvents under reduced pressure at 55°C afforded crude 12which on purification by column chromatography on silica gel using 20% acetone in hexane afforded solid which on recrystallisation in n-heptane afforded pure 12 as a white solid (5.0 g, 75 %).

IR: (KBr, cm−1) 3409 (NH); 1664 (C=O); 1219 (Ar C–N); 1384, 1459 (Ar C=C); 1055.7, 957.7 (Ar C–H). 1H NMR: (DMSO-d6) 0.96 (t, 3H,  = 9 . 0and 7.2 Hz, CH3); 1.35 (s, 6H, 2CH3); 1.54 (s, 6H, 2CH3); 1.66 (m, 2H, CH2); 2.55 (t, 2H, J= 7.5 and 7.5 Hz, CH2); 4.31 (m, 1H, OH); 4.99 (s, 2H, CH2); 7.12–7.54 (m, 5H, Ar-H), ESI-MS: (m/z): 489, mp: 62–66°C, Elemental analysis: calculated for C80H92N18O9: C, 66.37; H, 6.60; N, 17.20; O, 9.82; found: C, 66.42; H, 6.73; N, 17.32; O, 9.97.

Scheme 4: Synthesis of olmesartan medoxomil unknown impurity (12).

Figure 6: Proposed structures of “unknown impurity (12) (M/Z: 488.58).”

Journal of Chemistry
Volume 2013 (2013), Article ID 516459, 8 pages
http://dx.doi.org/10.1155/2013/516459

Research Article

Synthesis and Characterization of Process-Related Impurities of Antihypertensive Drug Olmesartan Medoxomil

G. Venkanna,1,2 G. Madhusudhan,1 K. Mukkanti,2 A. Sankar,1 Y. Sampath Kumar,1 and G. Venakata Narayana1

1Department of Research and Development, Inogent Laboratories Private Limited, 28A, IDA, Nacharam, Hyderabad 500 076, India
2Centre for Pharmaceutical Sciences, Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500 072, India

Received 18 February 2012; Accepted 17 May 2012

Academic Editor: Andreas G. Tzakos

Copyright © 2013 G. Venkanna et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

http://www.hindawi.com/journals/jchem/2013/516459/sch4/
Olmesartan medoxomil (1) is the latest angiotensin receptor antagonist approved by the FDA for the treatment of hypertension. During the process development of olmesartan medoxomil, three process-related impurities were observed along with the final API. These impurities were identified as isopropyl olmesartan (12), dimedoxomil olmesartan (19), dibiphenyl olmesartan (17). The present work describes the synthesis and characterization of all these three impurities.

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