A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib
Abstract Background Baricitinib, with a 2-(1-(ethylsulfonyl)azetidin-3-yl)acetonitrile moiety at N-2 position of the pyrazol skeleton, is an oral and selective reversible inhibitor of the JAK1 and JAK2 and displays potent anti-inflammatory activity. Several research-scale synthetic methods have been...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | BMC Chemistry |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13065-019-0639-y |
| _version_ | 1828786753227456512 |
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| author | Xin Cui Junming Du Zongqing Jia Xilong Wang Haiyong Jia |
| author_facet | Xin Cui Junming Du Zongqing Jia Xilong Wang Haiyong Jia |
| author_sort | Xin Cui |
| collection | DOAJ |
| description | Abstract Background Baricitinib, with a 2-(1-(ethylsulfonyl)azetidin-3-yl)acetonitrile moiety at N-2 position of the pyrazol skeleton, is an oral and selective reversible inhibitor of the JAK1 and JAK2 and displays potent anti-inflammatory activity. Several research-scale synthetic methods have been reported for the preparation of key quaternary heterocyclic intermediates of baricitinib. However, they were all associated with several drawbacks, such as the expensive materials, usage of pollutional reagents, and poor yields. Results In this manuscript, we established a green and cost-effective synthesis of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate for further scale-up production of baricitinib. This synthetic method employs commercially available and low-cost starting material benzylamine and an industry-oriented reaction of green oxidation reaction in microchannel reactor to yield important quaternary heterocyclic intermediates. Conclusion Generally, this procedure is reasonable, green and suitable for industrial production. |
| first_indexed | 2024-12-12T00:17:02Z |
| format | Article |
| id | doaj.art-28d8fe359bb44685b4c485a6aae9313f |
| institution | Directory Open Access Journal |
| issn | 2661-801X |
| language | English |
| last_indexed | 2024-12-12T00:17:02Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj.art-28d8fe359bb44685b4c485a6aae9313f2022-12-22T00:44:50ZengBMCBMC Chemistry2661-801X2019-10-011311710.1186/s13065-019-0639-yA green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinibXin Cui0Junming Du1Zongqing Jia2Xilong Wang3Haiyong Jia4Shandong Peninsula Engineering Research Center of Comprehensive Brine Utilization, Weifang University of Science and TechnologyShanghai Daozhen Pharmaceutical Technology Co., LTDShanghai Daozhen Pharmaceutical Technology Co., LTDShanghai Daozhen Pharmaceutical Technology Co., LTDSchool of Pharmacy, Weifang Medical UniversityAbstract Background Baricitinib, with a 2-(1-(ethylsulfonyl)azetidin-3-yl)acetonitrile moiety at N-2 position of the pyrazol skeleton, is an oral and selective reversible inhibitor of the JAK1 and JAK2 and displays potent anti-inflammatory activity. Several research-scale synthetic methods have been reported for the preparation of key quaternary heterocyclic intermediates of baricitinib. However, they were all associated with several drawbacks, such as the expensive materials, usage of pollutional reagents, and poor yields. Results In this manuscript, we established a green and cost-effective synthesis of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate for further scale-up production of baricitinib. This synthetic method employs commercially available and low-cost starting material benzylamine and an industry-oriented reaction of green oxidation reaction in microchannel reactor to yield important quaternary heterocyclic intermediates. Conclusion Generally, this procedure is reasonable, green and suitable for industrial production.http://link.springer.com/article/10.1186/s13065-019-0639-yBaricitinibJAK1/JAK2 inhibitorGreen synthesisMicrochannel reactor |
| spellingShingle | Xin Cui Junming Du Zongqing Jia Xilong Wang Haiyong Jia A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib BMC Chemistry Baricitinib JAK1/JAK2 inhibitor Green synthesis Microchannel reactor |
| title | A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib |
| title_full | A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib |
| title_fullStr | A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib |
| title_full_unstemmed | A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib |
| title_short | A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib |
| title_sort | green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib |
| topic | Baricitinib JAK1/JAK2 inhibitor Green synthesis Microchannel reactor |
| url | http://link.springer.com/article/10.1186/s13065-019-0639-y |
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