An Improved Economical Process for Preparation of Apremilast and Identified their Impurities

Y. Jagannadham; B. Ramadevi; B. Prasanna

doi:10.14233/ajchem.2016.20109

Issue

Vol. 28 No. 12 (2016): Vol 28 Issue 12

Issue Published : September 1, 2016

This work is licensed under a Creative Commons Attribution 4.0 International License.

An Improved Economical Process for Preparation of Apremilast and Identified their Impurities

https://doi.org/10.14233/ajchem.2016.20109

Y. Jagannadham

Research Center, Department of Chemistry, Chaitanya Post Graduate College (Autonomous), Hanamkonda, Warangal-506 001, India; College of Engineering, Jawaharlal Nehru Technological University, Hyderabad-500 085, India

B. Ramadevi

College of Engineering, Jawaharlal Nehru Technological University, Hyderabad-500 085, India

B. Prasanna

Corresponding Author(s) : B. Prasanna

prasschem@gmail.com

Asian Journal of Chemistry, Vol. 28 No. 12 (2016): Vol 28 Issue 12
Article Published : September 2, 2016

Abstract

The object of the present study is to provide an improved and commercially viable process for the preparation of apremilast, which is simple, cost effective and non-hazardous. In this process avoided the usage of acetic anhydride and high temperature. In this method, an alternative process using protected 3-aminophthalic acid (2) with acetyl chloride in the presence of triethanolamine as catalyst in dichloromethane solvent at 0 to 5 °C for 1 h. then followed by condensed with compound 3 to get the final compound 4. Besides, there were two unknown impurities like 3-(amino-1,3-dioxoisoindolin-2-yl)phthalic acid (5) and 4-aminoisobenzofuran-1,3-dione (6) identified by HPLC. A thorough study has been under taken to synthesize and characterize these unknown impurities. This improved process has a number of industrial advantages, such as economical material cost and relatively high yield. The structure of the synthesized compounds was elucidated by IR, ¹H NMR, ¹³C NMR, mass spectroscopy and elemental analyses.

Keywords

3-Amino phthalic acid Triethanolamine DCC Acetyl chloride

Jagannadham, Y., Ramadevi, B., & Prasanna, B. (2016). An Improved Economical Process for Preparation of Apremilast and Identified their Impurities. Asian Journal of Chemistry, 28(12), 2749–2751. https://doi.org/10.14233/ajchem.2016.20109

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References

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References

H.W. Man, P. Schafer, L.M. Wong, R.T. Patterson, L.G. Corral, H. Raymon, K. Blease, J. Leisten, M.A. Shirley, Y. Tang, D.M. Babusis, R. Chen, D. Stirling and G.W. Muller, J. Med. Chem., 52, 1522 (2009); doi:10.1021/jm900210d.

P.H. Schafer, A. Parton, A.K. Gandhi, L. Capone, M. Adams, L. Wu, J.B. Bartlett, M.A. Loveland, A. Gilhar, Y.-F. Cheung, G.S. Baillie, M.D. Houslay, H.-W. Man, G.W. Muller and D.I. Stirling, Br. J. Pharmacol., 159, 842 (2010); doi:10.1111/j.1476-5381.2009.00559.x.

K. Tasken and E.M. Aandahl, Physiol. Rev., 84, 137 (2004); doi:10.1152/physrev.00021.2003.

M. Conti and J. Beavo, Annu. Rev. Biochem., 76, 481 (2007); doi:10.1146/annurev.biochem.76.060305.150444.

M.D. Houslay, G.S. Baillie and D.H. Maurice, Circ. Res., 100, 950 (2007); doi:10.1161/01.RES.0000261934.56938.38.

M. Khobzaoui, H.J. Gutke and M. Burnet, Curr. Opin. Investig. Drugs, 6, 518 (2005).

A.B. Gottlieb, B. Strober, J.G. Krueger, P. Rohane, J.B. Zeldis, C.C. Hu and C. Kipnis, Curr. Med. Res. Opin., 24, 1529 (2008); doi:10.1185/030079908X301866.

K. Papp, C. Bolduc, P. Rohane, D. Sutherland, M. Jones and A. Hu, 66th Annual American Academy of Dermatology (AAD) Meeting, San Antonio, Texas, Feb. 1–5 (2008).

H.-W. Man, P. Schafer, L.M. Wong, R.T. Patterson, L.G. Corral, H. Raymon, K. Blease, J. Leisten, M.A. Shirley, Y. Tang, D.M. Babusis, R. Chen, D. Stirling and G.W. Muller, J. Med. Chem., 52, 1522 (2009);doi:10.1021/jm900210d.

G.W. Muller and H.-W. Man, Substituted Phenethylsulfones and Method of Reducing TNFa Levels, US Patent 6,020,358 (2000).

Issue

Vol. 28 No. 12 (2016): Vol 28 Issue 12

An Improved Economical Process for Preparation of Apremilast and Identified their Impurities

Corresponding Author(s) : B. Prasanna

Abstract

Keywords

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