Synthesis of(+)-ambrisentan

ZHANG Qingyang; LYU Jiuan; HU Haiyu

doi:10.11665/j.issn.1000-5048.20170307

Journal of China Pharmaceutical University > 2017 > 48(3): 293-296. > DOI: 10.11665/j.issn.1000-5048.20170307

ZHANG Qingyang, LYU Jiuan, HU Haiyu. Synthesis of(+)-ambrisentan[J]. Journal of China Pharmaceutical University, 2017, 48(3): 293-296. DOI: 10.11665/j.issn.1000-5048.20170307

Citation:

ZHANG Qingyang, LYU Jiuan, HU Haiyu. Synthesis of(+)-ambrisentan[J]. Journal of China Pharmaceutical University, 2017, 48(3): 293-296. DOI: 10.11665/j.issn.1000-5048.20170307

Citation:

ZHANG Qingyang, LYU Jiuan, HU Haiyu. Synthesis of(+)-ambrisentan[J]. Journal of China Pharmaceutical University, 2017, 48(3): 293-296. DOI: 10.11665/j.issn.1000-5048.20170307

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Synthesis of(+)-ambrisentan

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A five-step synthetic method of ambrisentan starting from benzophenone was developed. The reaction methods of resolution and substitution were optimized. A stable, facilitating method of detection and efficient resolution reagent, L-phenylglycinamide, was used and helped to obtain highly optical pure intermediates. In the substitution reaction, NaOH was chosen as the base, which is safe and suitable for the industry. This method was mild, easily operated with a total yield up to 31. 0%, and may have a good application prospect.
- ambrisentan,
- L-phenylglycinamide,
- resolution reagent,
- pulmonary arterial hypertension,
- synthesis,
- process improvement

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[1]	O′Callaghan DS,Savale L,Yaici A,et al.Endothenlin receptor antagonists for the treatment of pulmonary arterial hypertension[J].Expert Opin Pharmacother,2011,12(10):1585-1596.
[2]	Song JM,Wen XA,Sun HB.Progress in pathogensis and therapeutic drugs of pulmonary arterial hypertension[J].J China Pharm Univ(中国药科大学学报),2013,44(1):1-10.
[3]	Frampton JE.Ambrisentan[J].Am J Cardiovasc Drugs,2011,11(4):215-226.
[4]	Condliffe R,Elliot CA,Hurdman J,et al.Ambrisentan therapy in pulmonary hypertension:clinical use and tolerability in a referral centre[J].Ther Adv Respir Dis,2014,8(3):71-77.
[5]	Riechers H,Albrecht HP,Amberg W,et al.Discovery and optimization of a novel class of orally active nonpeptidic endothelin-a receptor antagonists[J].J Med Chem,1996,39(11):2123-2128.
[6]	Riechers H, Muller TW, Klinge D, et al. New carboxylic acid derivatives,their preparation and their use:WO,9611914A1[P].1996-04-25.
[7]	Li XG.Study on the synthesis of ambrisentan[J].Appl Chem Ind(应用化工),2014,43(9):1675-1678.
[8]	Liu AX,Chen YF,Yu YK,et al.Improved synthesis of ambrisentan[J].Chem Wor(化学世界),2011,52(2):100-102.
[9]	Jansen R,Knopp M,Amberg W,et al.Structural similarity and its surprises:endothelin receptor antagonists process reseach and development report[J].Org Process Res Dev,2001,5(1):16-22.
[10]	Nestl BM,Glueck SM,Hall M,et al.Biocatalytic racemization of(hetero)aryl-aliphatic α-hydroxycarboxylic acids by Lactobacillus spp.proceeds via an oxidation-reduction sequence[J].Eur J Org Chem,2006,2006(20):4573-4577.
[11]	Peng XY,Li PJ,Shi Y.Synthesis of(+)-ambrisentan via chiral ketone-catalyzed asymmetric epoxidation[J].J Org Chem,2012,77(1):701-703.

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