ChemicalBook CAS DataBase List Upadacitinib

Upadacitinib synthesis

4synthesis methods

Product Name:Upadacitinib
CAS Number:1310726-60-3
Molecular formula:C17H19F3N6O
Molecular Weight:380.37

Upadacitinib, also known as ABT-494, is a potent and selective JAK inhibitors in development for rheumatoid arthritis. ABT-494 is approximately 74 fold selective for Jak1 over Jak2 in cellular assays dependent on specific, relevant cytokines. ABT-494 demonstrates efficacy in rat arthritis models. Preliminary evidence suggests that compared to tofacitinib, ABT-494 may spare Jak2 and Jak3 dependent signaling. Synthetic Description Reference: Pangan, Aileen L.; Teixeira, Henrique D.; Allian, Ayman D.; Borchardt, Thomas B.; Jayanth, Jayanthy; Marroum, Patrick J.; Nordstrom, Fredrik Lars; Sheikh, Ahmad Y.; Mohamed, Mohamed-Eslam F.; Othman, Ahmed A.; Mayer, Peter T. Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof for disease treatment. Assignee AbbVie Inc., USA. US 20180298016. (2018). Synthetic Description Reference: Wishart, Neil; Argiriadi, Maria A.; Calderwood, David J.; Ericsson, Anna M.; Fiamengo, Bryan R.; Frank, Kristine E.; Friedman, Michael; George, Dawn M.; Goedken, Eric R.; Josephsohn, Nathan S.; Li, Biqin C.; Morytko, Michael J.; Stewart, Kent D.; Voss, Jeffrey W.; Wallace, Grier A.; Wang, Lu; Woller, Kevin R. Preparation of novel nitrogen-containing tricyclic compounds as kinase inhibitors. Assignee Abbott Laboratories, USA. US 20110311474. (2011).

Synthetic Routes

ROUTE 1

ROUTE 2

Reference: Pangan, Aileen L.; Teixeira, Henrique D.; Allian, Ayman D.; Borchardt, Thomas B.; Jayanth, Jayanthy; Marroum, Patrick J.; Nordstrom, Fredrik Lars; Sheikh, Ahmad Y.; Mohamed, Mohamed-Eslam F.; Othman, Ahmed A.; Mayer, Peter T. Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof for disease treatment. Assignee AbbVie Inc., USA. US 20180298016. (2018).

1428243-26-8 Synthesis

(3R,4S)-3-(2-Bromoacetyl)-4-ethyl-1-pyrrolidinecarboxylic acid phenylmethyl ester

1428243-26-8
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1310726-60-3
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Yield:-

Steps:

Multi-step reaction with 4 steps
1.1: lithium tert-butoxide / N,N-dimethyl acetamide / 0.5 h / -10 - 5 °C
1.2: 1 h / -10 °C
2.1: pyridine; trifluoroacetic anhydride / acetonitrile / 2 h / 75 °C
3.1: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 16 h / 50 °C / 1794.37 Torr
3.2: 1 h
4.1: tetrahydrofuran / 1.33 h / 30 °C
4.2: 1 h / 25 °C / pH 9

References:

US2017/129902,2017,A1

1201186-54-0 Synthesis