公开(公告)号：US12084460B2

公开(公告)日：2024-09-10

申请号：US17056351

申请日：2019-05-16

Applicant: NOVARTIS AG

Inventor： Nicole Bieri ,  Andreas Kordikowski ,  Bin Li ,  Philipp Lustenberger ,  Rita Ramos ,  Vijay Sethuraman ,  Sisi Zhang

IPC: A61K31/4162 ,  A61K31/5377 ,  A61K45/06 ,  C07D231/00 ,  C07D519/00 ,  A61K31/437 ,  C07D265/30 ,  C07D487/04

CPC classification number: C07D519/00 ,  A61K31/4162 ,  A61K31/5377 ,  A61K45/06 ,  C07D231/00 ,  A61K31/437 ,  C07B2200/13 ,  C07D265/30 ,  C07D487/04

Abstract: This application relates to various crystalline forms of (S)—N-(4-((5-(1,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide in its free form, as well as compositions, method of making and methods of using the same. In some embodiments the crystalline forms also contain water (“hydrates”). These materials are useful in the treatment of various autoimmune diseases, including systemic lupus erythematosus, cutaneous lupus, discoid lupus, mixed connective tissue disease, primary biliary cirrhosis, immune thrombocytopenia purpura, hidradenitis suppurativa, dermatomyositis, polymyositis, Sjögren's syndrome, arthritis, rheumatoid arthritis and psoriasis.

公开(公告)号：US11414411B2

公开(公告)日：2022-08-16

申请号：US16635596

申请日：2018-08-01

Applicant: Novartis AG

Inventor： Like Chen ,  Chi Ming Cheung ,  Zhongbo Fei ,  Qun Jiang ,  Lei Li ,  Bin Li ,  Thomas Ruch ,  Hao Wang ,  Quanbing Wu

IPC: C07D417/14

Abstract: The present invention provides a process of synthesizing 1-(((Z)-(1-(2-aminothiazol-4-yl)-2-oxo-2-(((3S,4R)-2-oxo-4-((2-oxooxazolidin-3-yl)methyl)-1-sulfoazetidin-3 yl)amino)ethylidene)amino)oxy)cyclopropanecarboxylic acid (referred to herein as Compound X), or a salt thereof, or a solvate including hydrate thereof, and/or intermediates thereof, and the use of intermediates for preparing Compound X. In particular, the process relates to the preparation of Compound X using dynamic kinetic resolution (DKR) and asymmetric catalytic reduction, thereby providing an improved route to 1-(((Z)-(1-(2-aminothiazol-4-yl)-2-oxo-2-(((3S,4R)-2-oxo-4-((2-oxooxazolidin-3-yl)methyl)-1-sulfoazetidin-3 yl)amino)ethylidene)amino)oxy)cyclopropanecarboxylic acid (Compound X) and compositions containing said compound, including the arginine salt, sodium salt and hydrated solid forms of Compound X.