1428243-27-9

Usage

Uses

Used in Pharmaceutical Industry:
(3R,4S)-benzyl 3-(2-(tert-butoxycarbonyl(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)amino)acetyl)-4-ethylpyrrolidine-1-carboxylate is used as a potential drug candidate for the development of new therapeutic agents, given its complex chemical structure and the presence of various functional groups that may contribute to its pharmacological properties. Further research and analysis are required to explore its full potential and applications in medicine.

Upstream product

• 13139-17-8 N-(Benzyloxycarbonyloxy)succinimide 
• 2445-93-4 ethyl 2-pentenoate 
• 51814-19-8 1-Benzyloxycarbonyl-4-ethoxycarbonyl-3-oxopyrrolidine 
• 1201186-54-0 2-bromo-5-(p-toluenesulfonyl)-5H-pyrrolo[2,3-b]pyrazine 
• 98-59-9 p-toluenesulfonyl chloride 
• 875781-41-2 5-bromo-3-((trimethylsilyl)ethynyl)pyrazine-2-amine 
• 1145-81-9 ethyl 2-(benzyloxycarbonylamino)ethanoate 
• 1268520-70-2 C₁₂H₂₁NO₄ 
• 24410-84-2 ethyl (2E)-pentenoate 

Downstream Products

• 1310726-60-3 (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 
• 1428243-28-0 8-((3R,4S)-4-ethylpyrrolidin-3-yl)-3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine 

Relevant academic research and scientific papers

Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib

Process development of a six-stage synthesis of upadacitinib, a JAK1 inhibitor, is described. It is highlighted by an enantioselective and diastereoselective hydrogenation of a tetrasubstituted olefin to set the two pyrrolidine stereocenters. Preparation of the main fragments and strategies to link them together, optimization of the imidazole cyclization, and in-depth understanding of the formation of the urea moiety at the final stage are discussed.

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF UPADACITINIB

The invention relates to a process for the preparation of compounds of formula (I), which are useful intermediates in the synthesis of Upadacitinib and structurally related compounds, by using Weinreb amide (III), or an equivalent thereof, as key intermediate.

Synthesis method of JAK (Janus Kinase) inhibitor

The invention discloses a synthesis method of a JAK (Janus Kinase) inhibitor. The synthesis method comprises the following steps: carrying out condensation on an intermediate A-8 and an intermediate B-3 to obtain an intermediate AB-1; carrying out deprotection on the intermediate AB-1 to obtain an intermediate AB-2; carrying out cyclization on the AB-2 to obtain an intermediate AB-3; carrying outthe deprotection on the intermediate AB-3 to obtain an intermediate AB-4; carrying out the deprotection on the AB-4 again to obtain an intermediate AB-5; carrying out condensation reaction on the AB-5to obtain the JAK inhibitor 1. The synthesis method disclosed by the invention has the main advantages that the intermediate A-8 is prepared through a chiral catalysis method in a high-yield and high-chiral-purity manner, and the intermediate B-3 and the JAK inhibitor 1 are prepared in a high-yield manner. Useless enantiomers are nearly not generated so that the pressure on the environment is reduced; meanwhile, the reaction yield is high, the operation is simple and the post-treatment is simple and convenient. According to the synthesis method, reaction conditions also can be applied to large-batch preparation and are suitable for industrial production, so that the synthesis method has relatively high practical value and social and economic benefits.

ALTERNATE PROCESSES FOR THE PREPARATION OF PYRROLIDINE DERIVATIVES

Aspects of the present application relate to process for the preparation of Pyrrolidine derivatives useful as key intermediates for active ingredients. Specific aspects relate to alternate process for the preparation of Upadacitinib intermediate, 4-ethylpyrrolidine-3-carboxylic acid, its ester or a salt thereof. Processes disclosed here in are cost effective and industrially viable as compared to known processes.

Upadacitinib tartrate: Tyrosine-protein kinase JAK1 inhibitor Treatment of autoimmune inflammatory diseases Treatment of rheumatoid arthritis

Upadacitinib tartrate (ABT-494) is a potent and selective tyrosine-protein kinase JAK1 inhibitor being developed for the treatment of systemic autoimmune inflammatory diseases, including rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis and psoriatic arthritis. In vitro, upadacitinib demonstrated higher selectivity for inhibiting JAK1 over JAK2 and JAK3, suggesting a potentially improved therapeutic profile in treating patients with inflammatory diseases compared to nonselective JAK inhibitors. Upadacitinib has demonstrated safety and efficacy in phase II trials in patients with RA and inflammatory bowel disease, and is currently in phase III development for these indications.

NOVEL TRICYCLIC COMPOUNDS

The invention provides compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.