- PROCESS AND INTERMEDIATES FOR PREPARING A JAK INHIBITOR
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The present invention is related to processes for preparing ruxolitinib, or a salt thereof, and related synthetic intermediates related thereto.
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- PROCESS FOR PREPARING ENANTIOMERICALLY ENRICHED JAK INHIBITORS
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Improved processes and intermediates for preparing ruxolitinib and deuterated analogs of ruxolitinib are disclosed.
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- SYNTHESIS PROCESS OF RUXOLITINIB
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The present application falls within the field of drug synthesis, and in particular, the present application relates to a method for preparing ruxolitinib, and a method for preparing the intermediate and relevant intermediates used. The method comprises reacting a compound of formula II with a compound of formula IV or a salt thereof to obtain a compound of formula III, and then subjecting the compound of formula III to an acyl halogenation reaction, an amidation reaction, and a reaction dehydrating an amide to form a cyano group or removing the protecting group to prepare ruxolitinib. The method has the characteristics of brief steps, a high stereoselectivity, a high utilization ratio of atoms, mild reaction conditions and convenient post treatment. The method avoids using expensive asymmetric reaction catalysts, and is suitable for industrial production.
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- Intermediate of JAK inhibitor, and preparation method thereof
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The present invention relates to a novel key intermediate of a JAK inhibitor ruxolitinib, and a preparation method thereof, wherein the chemical name of the intermediate is (R)-3-(4-boric acid-1H-pyrazole-1-yl)-3-cyclopentylpropionitrile. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield ofthe route is high, the purity of the obtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.
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- JAK PI3K/mTOR combination therapy
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Provided herein is a combination therapy comprising a JAK kinase inhibitor and a dual PI3K/mTOR inhibitor, as well as methods of treating various cancers through the use of such a combination therapy.
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Page/Page column 23
(2016/06/28)
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- SALT OF (R)-3-(4-(7H-PYRROLO [2,3-D] PYRIMIDIN-4-YL)-LH-PYRAZOL-L-YL)-3-CYCLOPENTYLPROPANENITRILE WITH BENZENESULFONIC ACID
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Provided herein are solid state forms of Ruxolitinib besylate, processes for preparing the solid state forms, as well as pharmaceutical compositions and formulations comprising said solid state forms.
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- PROCESSES FOR THE PREPARATION OF RUXOLITINIB PHOSPHATE
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The present invention relates to processes for the preparation of ruxolitinib and ruxolitinib phosphate. The present invention also provides a compound of Formula IV, processes for its preparation, and its use for the preparation of ruxolitinib and ruxolitinib phosphate. The present invention provides ruxolitinib phosphate having a chiral purity of 99.96% and the compound of Formula IV having a chiral purity of 99.95%.
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Page/Page column 29
(2016/03/19)
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- JANUS KINASE INHIBITORS FOR TREATMENT OF DRY EYE AND OTHER EYE RELATED DISEASES
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Methods, kits, and compositions for treating dry eye disorders and other related eye diseases are provided, wherein the methods, kits, and compositions utilize a JAK inhibitor.
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- THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR AND/OR A CDK 4/6 INHIBITOR
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Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a Janus kinase-2 (JAK-2) inhibitor, a cyclin-dependent kinase- 4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.
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- THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, AND/OR A BCL-2 INHIBITOR
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Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
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- Regio- and Enantioselective Synthesis of N-Substituted Pyrazoles by Rhodium-Catalyzed Asymmetric Addition to Allenes
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Abstract The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labelling experiments gave insights into the reaction mechanism. This new methodology was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)-ruxolitinib.
- Haydl, Alexander M.,Xu, Kun,Breit, Bernhard
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p. 7149 - 7153
(2015/06/08)
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- JAK P13K/mTOR COMBINATION THERAPY
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Provided herein is a combination therapy comprising a JAK kinase inhibitor and a dual PBK/mTOR inhibitor, as well as methods of treating various cancers through the use of such a combination therapy.
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- PROCESSES FOR PREPARING JAK INHIBITORS AND RELATED INTERMEDIATE COMPOUNDS
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The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.
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Page/Page column 79
(2010/08/07)
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- Enantioselective synthesis of janus kinase inhibitor INCB018424 via an organocatalytic aza-michael reaction
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An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3- cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.
- Lin, Qiyan,Meloni, David,Pan, Yongchun,Xia, Michael,Rodgers, James,Shepard, Stacey,Li, Mei,Galya, Laurine,Metcalf, Brian,Yue, Tai-N,Liu, Pingli,Zhou, Jiacheng
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supporting information; experimental part
p. 1999 - 2002
(2009/09/06)
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