Baricitinib, also known as INCB028050 or LY3009104, is a selective orally bioavailable JAK1/JAK2 inhibitor with nanomolar potency against JAK1 (5.9 nM) and JAK2 (5.7 nM). INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations <50 nM. INCB028050 was also effective in multiple murine models of arthritis, with no evidence of suppression of humoral immunity or adverse hematologic effects. Baricitinib was approved for the treatment of rheumatoid arthritis (RA) in the United States.
Synthetic Routes
Baricitinib - Synthetic Route 1
Synthetic Description
Reference: Xu, Jiaojiao; Cai, Jin; Chen, Junding; Zong, Xi; Wu, Xuan; Ji, Min; Wang, Peng. An efficient synthesis of baricitinib. Journal of Chemical Research. Volume 40. Issue 4. Pages 205-208. Journal. (2016).
Baricitinib - Synthetic Route 2
Synthetic Description
Reference: Anon. Crystalline forms in the preparation of 3-azetidineacetonitrile, 1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]. IP.com Journal. Volume 19. Issue 5A. Pages 1-3. Journal; Patent. (2019).
Reference: Zheng, Xuchun; Zhang, Yiping; Wu, Yihua. Process for synthesizing baricitinib compound as JAK inhibitor and intermediates. Assignee Hangzhou Cheminspire Technologies Co., Ltd., Peop. Rep. China. CN 106946917. (2017).
Baricitinib - Synthetic Route 5
Synthetic Description
Reference: Zhang, Feng; Che, Xiaoming; Huang, Xiaojing; Zhu, Suhua; Xue, Yuquan. Process for preparation of Baricitinib. Assignee Nanjing Yoko Pharmaceutical Co., Ltd., Peop. Rep. China; Nanjing Yoko Biopharmaceutical Research Co., Ltd.; Nanjing Yoko Biopharmaceutical Group Co., Ltd. CN 107176955. (2017).
Baricitinib - Synthetic Route 6
Synthetic Description
Reference: Simig, Gyula; Volk, Balazs; Katai Fadgyas, Katalin; Nagy, Tamas; Toth Lauritz, Maria; Sipos, Eva; Dancso, Andras; Szabo, Eva. Method and intermediate for the production of baricitinib. Assignee Egis Gyogyszergyar Zrt., Hung. WO 2017109524. (2017).
Baricitinib - Synthetic Route 7
Synthetic Description
Reference: Zheng, Xuchun; Zhang, Yiping; Wu, Yihua. A process for preparing baricitinib and its intermediates. Assignee Hangzhou Cheminspire Technologies Co., Ltd., Peop. Rep. China. CN 106496195. (2017).
Baricitinib - Synthetic Route 8
Synthetic Description
Reference: Kobierski, Michael Edward; Kopach, Michael E.; Martinelli, Joseph R.; Varie, David Lee; Wilson, Thomas Michael. Processes and intermediates for the preparation of {1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile. Assignee Eli Lilly and Company, USA. WO 2016205487. (2016).