New Process for Preparation of Dronedarone Hydrochloride

doi:10.7503/cjcu20120862

Abstract

Abstract:

Dronedarone hydrochloride(1), a potent blocker of multiple ion, was approved for atrial fibrillation by Food and Drug Administration(FDA) in 2009. It's a modified synthetic analogue of amiodarone, which decreases lipophilicity and results in a shorter lifetime and lower tissue accumulation. Here a new process for compound 1 was achieved with 33% overall yield starting from commercial p-aminophenol(2). N-(4-oxocyclohexa-2,5-dien-1-yl)-methanesulfonamide(4) which was obtained by mesylation and oxidization from compound 2 reacted with methyl 3-oxoheptanoate followed by cyclization to afford N--methanesulfonamide(6). The inversion of compound 6 into the desired compound 1 was realized by hydrolyzation and chlorination followed by Friedel-Crafts reaction with N-butyl-N-(3-phenoxypropyl)-1-butanamine hydrochloride. This process is characterized by cheap and readily available materials, shorter procedures, mild reaction conditions and convenient work-up, making it practical in industry.

Key words: Dronedarone hydrochloride, Antiarrhythmics, New process

CLC Number:

O626

TrendMD:

LI Feng, TIAN Shuan-Hong, SONG Xiao-Feng, LI Wen-Yuan, CHENG Hua-Ying, LEI Ling-Zhi, ZHU Qin-Feng, JIN Chun-Hua, LI Shao-Hua. New Process for Preparation of Dronedarone Hydrochloride[J]. Chem. J. Chinese Universities, 2013, 34(4): 858.

References

[1] Kuzniatsova N., Pamukcu B., Lip G. Y. H., Therapy, 2011, 8(6), 681—689

[2] Patel P. B., Patel K. C., Mehta H. R., Int. Res. J. Pharm, 2011, 2(3), 59—65

[3] Patel P. D., Bhuriya R., Patel D. D., Arora B. L., Singh P. P., Arora R. R., Vasc. Health Risk Manage, 2009, 5, 635—642

[4] Dobromir D., Stanley N., Lancet, 2010, 375, 1212—1223

[5] Singh B. N., Capucci A., Radzik D., Hohnloser S. N., Engl. J. Med., 2007, 357, 987—999

[6] Gubin J., Lucchetti J., Inion H., Chatelain P., Rosseels G., Kilenyi S., Preparation of Benzofurans, Benzothiophenes, Indoles, and Indolizines as Cardiovascular Agent, EP 0471609, 1991-08-06

[7] Biard M., 2-Butyl-3-(4-Benzoyl)-5-Nitro-Benzofuran Hydrochlorides and Preparation Thereof, WO 2002048078, 2001-12-10

[8] Fino N., Leroy C., A Process for the Preparation of 2-Butyl-5-Benzofuran as an Intermediate for the Synthesis of Dronedarone,WO 2002048132, 2001-12-10

[9] Gutman A., Nisnevich G., Yudovitch L., Process for the Preparation of Dronedarone, WO 2003040120, 2002-11-06

[10] Eklund L., Process for the Preparation of Benzofuran via Cyclocondensation of Phenylhydroxylamines with Ketones, WO 2009044143, 2008-10-02

[11] Fu Q. Q., Yang T. B., Zhao M. X., Novel Method for Preparing Dronedarone, CN 101993427, 2009-08-26(付清泉, 杨涛波, 赵茂先. 一种制备决奈达隆的新方法, CN 101993427, 2009-08-26)

[12] Friesz A., Dombrady Z., Csatarine N. M., Process for Preparation of Dronedarone, WO 2011070380, 2010-11-23

[13] Friesz A., Csatarinenagy M., An Improved Process for the Preparation of Dronedarone via Novel Intermediates, WO 2011083346, 2010-12-15

[14] Zhai F. M., Chen Y. J., Hu Q., Method for Preparation of Antiarrhythmic Drug Dronedarone, CN 102180848, 2010-12-31(翟富民, 陈拥军, 胡全. 一种新型抗心律失常药决奈达隆的制备方法, CN 102180848, 2010-12-31)

[15] Sada M., Nardi A., Maiorana S., Novel Process for the Manufacture of Dronedarone, WO 2011104591, 2011-01-26

[16] Giri R. L., Mohite V. D., Kambhampati S., Chitturi T. R., Thennati R., A Process for the Preparation of Butyldibutylaminopropoxyenzoylbenzofuranylmethanesulfonamide Hydrochloride, WO 2012120544, 2012-09-13

[17] Hivarekar R. R., Deshmukh S. S., Tripathy N. K., Org. Process Res. Dev., 2012, 16(4), 677—681

[18] Baragona F., Lomberget T., Lo P. E., Barret R., Diana P., Montalbano A., Duchamp C., Henriques N., J. Med. Chem., 1999, 42(6), 1041—1052

[19] Baragona F., Tetrahedron, 2011, 67(45), 8731—8739

[20] Payne J. E., Smith N. D., Parent S. D., Lei W., Salts of Pyridine Derivatives as Inhibitors Histone Deacetylase and Their Preparation, Pharmaceutical Compositions and Use in the Treatment of Disease, WO 2008073733, 2008-06-19

[21] Gibbs C. F., J. Am. Chem. Soc., 1934, 56(3), 725—727

[22] Adams R., Looker J. H., J. Am. Chem. Soc., 1951, 73(3), 1145—1149

[23] Wang Y., Frank S. G. J., J. Org. Chem., 2001, 66(25), 8293—8296