Title:
INTERMEDIATE OF EDOXABAN TOSYLATE AND PREPARATION METHOD THEREFOR
Document Type and Number:
WIPO Patent Application WO/2023/108602
Kind Code:
A1
Abstract:
Disclosed are an intermediate of edoxaban tosylate and a preparation method therefor, having the advantages that the preparation process is simple, reaction conditions are mild, the cost is low, and raw materials are easy to obtain. The method comprises the synthesis steps of: subjecting a compound N-methyl-4-piperidone, as a raw material, to a substitution reaction with bromine to generate a compound represented by formula (II); subjecting the compound represented by formula (II) to a thiolation reaction with sodium sulfide to obtain a compound represented by formula (III); subjecting the compound represented by formula (III) to a cyclization reaction with glyoxylic acid to obtain a compound represented by formula (IV); subjecting the compound represented by formula (IV) to an esterification reaction with alcohol to obtain a compound represented by formula (V), and then reacting to obtain a compound represented by formula (VI), or directly reacting the compound represented by formula (IV) under the effect of alcohol and acid, to obtain the compound represented by formula (VI); and subjecting the compound represented by formula (VI) to alkali hydrolysis and acid neutralization to obtain a compound represented by formula (VII). The reaction formula is as follows.
Inventors:
MEI YIJIANG (CN)
LIU SHENGMIN (CN)
LI YONGGANG (CN)
FAN JINMIN (CN)
HU KAI (CN)
GAO SHIZHAO (CN)
LIU SHENGMIN (CN)
LI YONGGANG (CN)
FAN JINMIN (CN)
HU KAI (CN)
GAO SHIZHAO (CN)
Application Number:
PCT/CN2021/139089
Publication Date:
June 22, 2023
Filing Date:
December 17, 2021
Export Citation:
Assignee:
ZHEJIANG JIUZHOU PHARM CO LTD (CN)
International Classes:
C07D513/04; C07D211/74
Foreign References:
| CN106459087A | 2017-02-22 | |||
| CN103140466A | 2013-06-05 | |||
| US20050119486A1 | 2005-06-02 |
Other References:
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DATABASE Registry CAS; 4 December 2015 (2015-12-04), ANONYMOUS : "Thiazolo[5,4-c]pyridine-2 -carboxylic acid, 3a,4,5,6,7,7a-hexahy dro-5-methyl-", XP093072574, retrieved from STNext Database accession no. 1822565-65-0
MOCHIZUKI, AKIYOSHI ET AL.: "Design, synthesis, and biological activity of piperidine diamine derivatives as factor Xa inhibitor", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 18, 17 November 2007 (2007-11-17), XP022424748, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2007.11.037
DATABASE Registry CAS; 14 September 2015 (2015-09-14), ANONYMOUS : "Thiazolo[5,4-c]pyridine-2 -carboxylic acid, 4,5, 6,7-tetrahydro-5-met hyl-, 4-(trifluoromethyl)p henyl ester", XP093072576, retrieved from STNext Database accession no. 1807316-03-5
DATABASE Registry CAS; 3 November 2016 (2016-11-03), ANONYMOUS : "Thiazolo[5,4-c]pyridine-2 -carboxylic acid, 4,5, 6,7-tetrahydro-5-met hyl-, 1,1-dimethylethyl es ter ", XP093072577, retrieved from STNext Database accession no. 2024144-14-5
Attorney, Agent or Firm:
ZHEJIANG KG IP LAW FIRM (CN)
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