Title:
PREPARATION METHOD FOR HALOFUGINONE INTERMEDIATE TRANS-N-BENZYLOXYCARBONYL-(3-HYDROXY-2-PIPERIDINYL)-2-ACETONE
Document Type and Number:
WIPO Patent Application WO/2023/065610
Kind Code:
A1
Abstract:
The present invention relates to the field of drug synthesis. Disclosed is a preparation method for halofuginone intermediate trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone. The preparation method of the present invention comprises: first using animo-substituted valeraldehyde and a thiazole sulfoxide compound as raw materials, carrying out an Mislow-Evans rearrangement reaction, and then preparing trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone shown in formula I under the catalysis of Lewis acid. The preparation method for halofuginone intermediate trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone of the present invention is high in yield and stable in quality, provides a new route reference for the synthesis of trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone, avoids the reduction of pyridine, and overcomes the defect that an expensive Rh/Al2O3 metal catalyst needs to be used.
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Inventors:
FENG YU (CN)
XU HONG (CN)
WU JIA-YI (CN)
SONG DAN-HUI (CN)
ZHONG WEI-HUI (CN)
LING FEI (CN)
XU CHAO (CN)
XU HONG (CN)
WU JIA-YI (CN)
SONG DAN-HUI (CN)
ZHONG WEI-HUI (CN)
LING FEI (CN)
XU CHAO (CN)
Application Number:
PCT/CN2022/086077
Publication Date:
April 27, 2023
Filing Date:
April 11, 2022
Export Citation:
Assignee:
CHENGDA PHARMACEUTICALS CO LTD (CN)
International Classes:
C07C269/06; C07D211/42; C07C271/18
Foreign References:
| CN113999164A | 2022-02-01 | |||
| CN110452158A | 2019-11-15 | |||
| CN103467449A | 2013-12-25 |
Other References:
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CHU QIAN, DIEDRICH JOLENE K., VAUGHAN JOAN M., DONALDSON CYNTHIA J., NUNN MICHAEL F., LEE KUO-FEN, SAGHATELIAN ALAN: "HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 138, no. 30, 3 August 2016 (2016-08-03), pages 9473 - 9478, XP093058022, ISSN: 0002-7863, DOI: 10.1021/jacs.6b03463
SUKEMOTO SATOSHI, OSHIGE MIYO, SATO MASAHIRO, MIMURA KEN-ICHIRO, NISHIOKA HIROMI, ABE HITOSHI, HARAYAMA TAKASHI, TAKEUCHI YASUO: "Concise Asymmetric Synthesis of (+)-Febrifugine Utilizing trans- Selective Intramolecular Conjugate Addition", SYNTHESIS, GEORG THIEME VERLAG, STUTTGART, DE., vol. 2008, no. 19, 1 October 2008 (2008-10-01), STUTTGART, DE. , pages 3081 - 3087, XP093058023, ISSN: 0039-7881, DOI: 10.1055/s-2008-1067271
NOKAMI, J. ET AL.: "Convenient Formation of 4-Hydroxyalk-2-en-1-one Functionality via A Knoevenagel-type Carbon Chain Elongation Reaction of Aldehyde with 1-Arylsulfinylalkan-2-one.", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 66, no. 4, 31 January 2001 (2001-01-31), pages 1228 - 1232, XP001001777, ISSN: 0022-3263, DOI: 10.1021/jo001323g
DU, Z. J. ET AL.: "Alkyl 2-(2-benzothiazolylsulfinyl)acetates as useful synthetic reagents for alkyl 4-hydroxyalk-2-enoates by sulfinyl-Knoevenagel reaction.", TETRAHEDRON., vol. 68, no. 11, 24 January 2012 (2012-01-24), XP028459386, ISSN: 0040-4020, DOI: 10.1016/j.tet.2012.01.057
CHU QIAN, DIEDRICH JOLENE K., VAUGHAN JOAN M., DONALDSON CYNTHIA J., NUNN MICHAEL F., LEE KUO-FEN, SAGHATELIAN ALAN: "HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 138, no. 30, 3 August 2016 (2016-08-03), pages 9473 - 9478, XP093058022, ISSN: 0002-7863, DOI: 10.1021/jacs.6b03463
SUKEMOTO SATOSHI, OSHIGE MIYO, SATO MASAHIRO, MIMURA KEN-ICHIRO, NISHIOKA HIROMI, ABE HITOSHI, HARAYAMA TAKASHI, TAKEUCHI YASUO: "Concise Asymmetric Synthesis of (+)-Febrifugine Utilizing trans- Selective Intramolecular Conjugate Addition", SYNTHESIS, GEORG THIEME VERLAG, STUTTGART, DE., vol. 2008, no. 19, 1 October 2008 (2008-10-01), STUTTGART, DE. , pages 3081 - 3087, XP093058023, ISSN: 0039-7881, DOI: 10.1055/s-2008-1067271
NOKAMI, J. ET AL.: "Convenient Formation of 4-Hydroxyalk-2-en-1-one Functionality via A Knoevenagel-type Carbon Chain Elongation Reaction of Aldehyde with 1-Arylsulfinylalkan-2-one.", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 66, no. 4, 31 January 2001 (2001-01-31), pages 1228 - 1232, XP001001777, ISSN: 0022-3263, DOI: 10.1021/jo001323g
Attorney, Agent or Firm:
JIAXING QIFAN PATENT AGENCY (GENERAL PARTNERSHIP) (CN)
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