Improved synthetic approach: route A (feasibility) and B (after optimization)
Rakeshwar Bandichhor Ph.D. FRSC, CChem, SSWB,BB,MB
Director at Dr. Reddy’s Laboratories, Vice-Chair, ACS-India Chapter (South India)
They have developed an improved process for pioglitazone which appears to be more compatible with industrial scale and has some advantages over the existing synthesis.
Preparation of Pioglitazone Hydrochloride (1·HCl) salt
1H NMR (400 MHz, DMSO-d6) 12.08 (s, 1H), 8.73 (d, 1H, J = 1.6 Hz), 8.43 (dd, 1H, J = 2.0, 8.0 Hz), 8.01 (d, 1H, J = 8.0 Hz), 7.16 (d, 2H, J = 8.8 Hz), 6.89 (d, 2H, J = 8.8 Hz), 4.88 (dd, 1H, J = 4.4, 8.8 Hz), 4.34 (t, 2H, J = 6.2 Hz), 3.55 (t, 2H, J = 6.2 Hz), 3.30 (dd, 1H, J = 4.4, 14.0 Hz), 3.06 (dd, 1H, J = 8.8, 14.0 Hz), 2.80 (q, 2H, J = 7.6 Hz), 1.24 (t, 3H, J = 7.6 Hz); 13C NMR (400 MHz, DMSO-d6) 175.6, 171.5, 156.9, 151.0, 145.2, 141.3, 139.8, 130.3, 129.0, 127.1, 114.4, 65.4, 52.8, 40.1, 39.9, 39.7, 39.5, 39.2, 39.0, 38.8, 36.2, 32.1, 24.5, 14.5; IR (KBr) 2928, 2742, 1743, 1694, 1616, 1510, 1461, 1313, 1243, 1038, 850, 712 cm−1; HRMS (Cl) calcd For C19H20N3O3S (M+) 356.44; found (MH+) 357.5.
An Improved Process for Pioglitazone and Its Pharmaceutically Acceptable Salt†
Innovation Plaza, IPD, R&D, Dr. Reddy’s Laboratories Ltd., Survey Nos. 42, 45,46, and 54, Bachupally, Qutubullapur, R.R. District – 500 073, Andhra Pradesh, India, and Institute of Science and Technology, Center for Environmental Science, JNT University, Kukatpally, Hyderabad – 500 072, Andhra Pradesh, India
Org. Process Res. Dev., 2009, 13 (6), pp 1190–1194
DOI: 10.1021/op900131m
†DRL-IPD Communication number: IPDO-IPM-00169.
, * Corresponding author. E-mail: rakeshwarb@drreddys.com. Telephone: +91 4044346000. Fax: +91 4044346285.,
, * Corresponding author. E-mail: rakeshwarb@drreddys.com. Telephone: +91 4044346000. Fax: +91 4044346285.,
‡Innovation Plaza, IPD, R&D, Dr. Reddy’s Laboratories Ltd.
, §Institute of Science and Technology, Center for Environmental Science, JNT University.
Abstract
An improved process for pioglitazone (1) is described. The process features high-yielding transformations employing inexpensive reagents and recoverable solvents.
link is
http://pubs.acs.org/doi/full/10.1021/op900131m
The original paper in OPRD is interesting example of process improvement
References
http://shodhganga.inflibnet.ac.in/bitstream/10603/19311/9/09_chapter%201.pdf
///////////
