- NOVEL PROCESS FOR THE PREPARATION OF FILGOTINIB AND INTERMEDIATES THEREOF
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The present invention relates to a novel process for the preparation of filgotinib or a pharmaceutically acceptable salt and intermediates thereof which avoid Suzuki coupling reaction. (I)
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- Preparation method of filgotinib
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A preparation method of filgotinib comprises the following steps: directly carrying out suzuki coupling on a compound of formula 1 and 4-formylphenylboronic acid, reacting the obtained reaction product with cyclopropylformylchloride to obtain a compound of formula 4, carrying out a reductive amination reaction on the compound of formula 4 and thiomorpholine 1,1-dioxide or its hydrochloride, and hydrolyzing the obtained reaction product to obtain the phenatinib product 9; or coupling the compound of formula 1 with cyclopropylformylchloride, reacting the obtained reaction product with 4-formylphenylboronic acid, and performing the reductive amination reaction on the obtained reaction product and thiomorpholine 1,1-dioxide to obtain the filgotinib product 9. The method widens the substrate range, increases the route efficiency, reduces the process cost, and achieves the effects of reducing the generation of byproducts and improving the purity of the final product by improving the crystallization property of intermediates in the route; and the route is simple to operate, the total yield is high, and the purity of the obtained product is high, so the method is suitable for large-scale production.
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Paragraph 0088-0091
(2020/03/23)
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- PROCESSES FOR THE PREPARATION OF FILGOTINIB
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The present invention relates to processes for the preparation of Filgotinib. The present invention relates to novel processes for the preparation of filgotinib. The present invention also relates to novel intermediates for the preparation of filgotinib.
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- Synthesis method of JAK1 inhibitor Filgotinib
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The invention provides a preparing method of Filgotinib. The preparing method comprises the following steps that (1), 2-amino-6-bromopyridine reacts with a p-methylbenzene derivative to prepare a compound 1; (2), the compound 1 reacts with ethoxycarbonyl
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- [1,2,4]triazol[1,5-a]pyridine compound as well as preparation method and medical application thereof
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The invention relates to a [1,2,4]triazol[1,5-a] pyridine compound as well as a preparation method and medical application thereof. Particularly, the invention relates to the compound shown in a general formula I, the preparation method of the compound, a
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- SOLID FORMS OF FILGOTINIB FREE BASE
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The present invention relates to crystalline filgotinib free base, a method of its preparation and a pharmaceutical composition comprising the same.
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Page/Page column 29; 30
(2017/02/23)
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- A Filgotinib synthetic method
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The invention discloses a filgotinib synthetic method and belongs to the technical field of chemical synthesis of medicines. 6-chloro-2-aminopyridine and di-tert-butyl dicarbonate ester are subjected to condensation reaction to obtain 6-chloro-2-tert-butyloxycarbonyl aminopyridine; hydrolysis reaction is performed; the obtained 6-chloro-2-tert-butyloxycarbonyl aminopyridine and trifluorinated methyl sulfonic anhydride are subjected to trifluoromethanesulfonic acid esterification reaction; the obtained 2-tert-butyloxycarbonylamino-6-pyridyltrifluoromethanesulfonate and [(1,1-dioxo-4-thiomorpholinyl)methyl]benzo-4-boronic acid pinacol ester are subjected to condensation reaction to obtain a tert-butyl ester derivative; the tert-butyl ester derivative is treated by trifluoroacetic acid and subjected to de-protection; the obtained intermediate and ethoxycarbonyl isothiocyanate are subjected to isothiocyanate reaction; the obtained intermediate and hydroxylamine hydrochloride are subjected to ring closing reaction; the obtained intermediate and cyclopropane carbonyl chloride are subjected to amidation reaction to obtain the finished product. Operation is simplified; reagents are available; the concept of environment friendliness and environment protection is embodied.
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- CRYSTALLINE FILGOTINIB SULFONIC ACID ADDITION SALTS
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The present invention relates to filgotinib sulfonic acid addition salts, their polymorphs, a method of preparing the same as well as a pharmaceutical composition comprising the same.
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Page/Page column 33-34
(2017/02/09)
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- METHODS FOR THE TREATMENT OF CARDIOVASCULAR DISORDERS
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The present invention discloses compounds according to Formula (I): or a pharmaceutically acceptable salt thereof, or a solvate or the salt of a solvate thereof, pharmaceutical compositions comprising the same, and methods of treatment using the same, for
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- PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF INFLAMMATORY DISORDERS
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The present invention discloses pharmaceutical compositions comprising: a compound according to Formula I: useful in the prophylaxis and/or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, d
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- NOVEL SALTS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS
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The present invention discloses salts of a Compound 1: useful in the prophylaxis and/or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and/or disruption of
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- FILGOTINIB: Tyrosine-protein kinase JAK1 inhibitor, treatment of rheumatoid arthritis, treatment of crohn's disease
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Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, is associated with pain, progressive disability, systemic comorbidities and early death. Filgotinib (GLPG-0634), a new selective tyrosine-protein kinase (JAK1) inhibitor, is currently i
- Gras
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p. 547 - 551
(2014/12/11)
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- Triazolopyridines as selective JAK1 inhibitors: From hit identification to GLPG0634
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Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified
- Menet, Christel J.,Fletcher, Stephen R.,Van Lommen, Guy,Geney, Raphael,Blanc, Javier,Smits, Koen,Jouannigot, Nolwenn,Deprez, Pierre,Van Der Aar, Ellen M.,Clement-Lacroix, Philippe,Lepescheux, Liên,Galien, René,Vayssiere, Béatrice,Nelles, Luc,Christophe, Thierry,Brys, Reginald,Uhring, Muriel,Ciesielski, Fabrice,Van Rompaey, Luc
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p. 9323 - 9342
(2015/01/09)
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- NOVEL COMPOUND USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES
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A novel compound able to inhibit JAK is disclosed, this compound may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting exa
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Page/Page column 13-14
(2011/01/05)
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