Title:
METHOD FOR SYNTHESIZING HIV PROTEASE INHIBITOR INTERMEDIATE COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2021/036256
Kind Code:
A1
Abstract:
The present application is suitable for use in the technical field of drug synthesis, and provides a method for synthesizing an HIV protease inhibitor intermediate compounds. The method comprises subjecting compound 1a to an asymmetric transfer hydrogenation reaction by adding a catalyst mixture and a hydrogen source in a reaction solvent under argon protection to obtain intermediate compounds 2a and 2a' for an HIV protease inhibitor, wherein the synthesis route thereof is as shown in (I), in which the R group is one of tert-butoxycarbonyl, benzyloxycarbonyl, p-toluenesulfonyl, acetyl, or a benzoyl group. The asymmetric transfer hydrogenation technique adopted in the present application provides the synthesized HIV protease inhibitor intermediate compounds having significantly increased stereoselectivity and yield in comparison to similar existing intermediates, with a diastereoselectivity ratio of the product reaching 94:6. Moreover, the catalyst is used in a small amount but has a high catalytic efficiency, reaction activity is improved, raw material wastage is reduced, the whole process is fast and convenient, and the cost is low.
Inventors:
LANG QIWEI (CN)
DING XIAOBING (CN)
GAO SHUANG (CN)
DING XIAOBING (CN)
GAO SHUANG (CN)
Application Number:
PCT/CN2020/082630
Publication Date:
March 04, 2021
Filing Date:
March 31, 2020
Export Citation:
Assignee:
SHENZHEN CATALYS TECH CO LTD (CN)
International Classes:
C07C271/16; C07C27/04; C07C27/06; C07C29/143; C07C33/46; C07C231/12; C07C231/16; C07C231/18; C07C233/04; C07C269/06; C07C311/16; C07C315/04
Foreign References:
| US20040082820A1 | 2004-04-29 | |||
| CN104024218A | 2014-09-03 | |||
| US20100022795A1 | 2010-01-28 |
Other References:
FANGYUAN WANG ET AL.: "Rh(III)-Catalyzed Diastereoselective Transfer Hydrogenation: an Efficient Entry to Key Intermediates of HIV Protease Inhibitors.", CHEM. COMMUN., vol. 56, no. 21, 22 February 2020 (2020-02-22), pages 3119 - 3122, XP055785844, ISSN: 1359-7345
TAKAYUKI HAMADA ET AL.: "Asymmetric Transfer Hydrogenation of α-Aminoalkyl α'-Chloromethyl Ketones with Chiral Rh Complexes.", JOURNAL OF ORGANIC CHEMISTRY, vol. 69, no. 21, 17 September 2004 (2004-09-17), XP055785846, ISSN: 0022-3263
LONG-SHENG ZHENG ET AL.: "Rhodium-Mediated Asymmetric Transfer Hydrogenation: a Diastereo- and Enantioselective Synthesis of Syn-α-amido β-Hydroxy Esters.", CHEMICAL COMMUNICATIONS, vol. 54, no. 3, 7 December 2017 (2017-12-07), pages 283 - 286, XP055785849, ISSN: 1359-7345
TAKAYUKI HAMADA ET AL.: "Asymmetric Transfer Hydrogenation of α-Aminoalkyl α'-Chloromethyl Ketones with Chiral Rh Complexes.", JOURNAL OF ORGANIC CHEMISTRY, vol. 69, no. 21, 17 September 2004 (2004-09-17), XP055785846, ISSN: 0022-3263
LONG-SHENG ZHENG ET AL.: "Rhodium-Mediated Asymmetric Transfer Hydrogenation: a Diastereo- and Enantioselective Synthesis of Syn-α-amido β-Hydroxy Esters.", CHEMICAL COMMUNICATIONS, vol. 54, no. 3, 7 December 2017 (2017-12-07), pages 283 - 286, XP055785849, ISSN: 1359-7345
Attorney, Agent or Firm:
SHENZHEN LANFENG SHENGSHI INTELLECTUAL PROPERTY AGENCY CO., LTD (CN)
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