Title:
PREPARATION METHOD FOR HIGH PURITY LIRAGLUTIDE SIDE CHAIN
Document Type and Number:
WIPO Patent Application WO/2020/182227
Kind Code:
A1
Abstract:
Disclosed is a preparation method for high purity liraglutide side chain, comprising: using palmitic acid, N-hydroxysuccinimide and N,N'-diisopropylcarbodiimide as reaction starting materials, and sequentially obtaining Palmitoyl-OSu, Palmitoyl-Glu-OtBu and liraglutide side chain crude product Palmitoyl-Glu(OSu)-OtBu; filtering the reaction solution, washing the resulting filtrate with an acidic aqueous solution, and concentrating the organic phase until dry; recrystallizing the organic phase with an alkane, a fatty alcohol or a mixed solvent thereof to obtain high purity liraglutide side chain. The preparation method for high purity liraglutide side chain has a simple operation, a short synthesis cycle, low costs and easy post-processing, the product purity can reach up to 99.41%, and HOSU, DIU, myristic acid, L5-S2 and stearic acid impurities, as well as other unknown impurities, can be effectively removed, which is beneficial for mass production.
Inventors:
CHENG LIHUA (CN)
WANG YIN (CN)
XU YONGGANG (CN)
CHEN SONG (CN)
ZHANG HAONING (CN)
WANG YIN (CN)
XU YONGGANG (CN)
CHEN SONG (CN)
ZHANG HAONING (CN)
Application Number:
PCT/CN2020/088481
Publication Date:
September 17, 2020
Filing Date:
April 30, 2020
Export Citation:
Assignee:
AMPHASTAR NANJING PHARMACEUTICALS INC (CN)
NANJING HANXIN PHARMACEUTIAL TECH CO LTD (CN)
NANJING HANXIN PHARMACEUTIAL TECH CO LTD (CN)
International Classes:
C07D207/46
Domestic Patent References:
| WO2005082404A2 | 2005-09-09 |
Foreign References:
| CN109836368A | 2019-06-04 | |||
| CN106146647A | 2016-11-23 | |||
| CN1951965A | 2007-04-25 | |||
| CN1705681A | 2005-12-07 | |||
| CN103980358A | 2014-08-13 |
Other References:
IVAN GURYANOV , ALEX BONDESAN , DARIO VISSENTINI , ANDREA ORLANDIN , BARBARA BLONDI , CLAUDIO TONIOLO , FERNANDO FORMAGGIO , ANTON: "Innovative chemical synthesis and conformational hints on the lipopeptide liraglutide", JOURNAL OF PEPTIDE SIENCE, vol. 22, no. 7, 30 May 2016 (2016-05-30), pages 471 - 479, XP002761314, ISSN: 1075-2617, DOI: 10.1002/psc.2890
QIU, BINGYI: "Section 1, Higher Fatty Acid", COMPLETE WORKS ON COSMETICS AND PROCESS TECHNOLOGY, 31 January 2000 (2000-01-31), pages 77 - 80, XP009523115, ISBN: 9787501920709
WANG, ZHONGHUA ET AL: " 5-myristic acid", OILFIELD CHEMICALS MANUAL, 31 July 2004 (2004-07-31), pages 256 - 260, XP009523116, ISBN: 7-80164-529-4
QIU, BINGYI: "Section 1, Higher Fatty Acid", COMPLETE WORKS ON COSMETICS AND PROCESS TECHNOLOGY, 31 January 2000 (2000-01-31), pages 77 - 80, XP009523115, ISBN: 9787501920709
WANG, ZHONGHUA ET AL: " 5-myristic acid", OILFIELD CHEMICALS MANUAL, 31 July 2004 (2004-07-31), pages 256 - 260, XP009523116, ISBN: 7-80164-529-4
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