- Regioselective Synthesis of Pyrazolo[1,5- a]pyridine via TEMPO-Mediated [3 + 2] Annulation-Aromatization of N-Aminopyridines and α,β-Unsaturated Compounds
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A TEMPO-mediated [3 + 2] annulation-aromatization protocol for the preparation of pyrazolo[1,5-a]pyridines from N-aminopyridines and α,β-unsaturated compounds was developed. The procedure offered multisubstituted pyrazolo[1,5-a]pyridines in good to excellent yield with high and predictable regioselectivity. The modification of marketed drugs including Loratadine, Abiraterone, and Metochalcone, and a one-pot three-step gram scale synthesis of key intermediate for the preparation of Selpercatinib were demonstrated. Mechanism studies show that TEMPO serves both as a Lewis acid and as an oxidant.
- Wang, Amu,Liu, Ya-Zhou,Shen, Zhongke,Qiao, Zeen,Ma, Xiaofeng
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supporting information
p. 1454 - 1459
(2022/03/01)
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- Pyrazolopyridine derivatives for regulating synthesis activity of estrogen receptor
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The invention relates to the technical field of organic chemistry and medicinal chemistry, and in particular, relates to pyrazolopyridine derivatives for regulating the synthesis activity of an estrogen receptor. According to the specific technical scheme, under the alkaline condition, substituted 1-aminopyridine and an alpha,beta-unsaturated compound are stirred together in the presence of an oxidizing agent, and the substituted pyrazol[1,5-a]pyridine compounds are formed. A one-step synthesis strategy is adopted, the alpha,beta-unsaturated compound is used as a raw material, and a series of pyrazol[1,5-a]pyridine compounds are efficiently and highly selectively synthesized in the presence of an organic oxidant.
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Paragraph 0126-0137
(2021/09/15)
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- Compound used as RET kinase inhibitor and application thereof
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The invention relates to a compound used as an RET kinase inhibitor and application thereof, wherein the compound has a structure as shown in a formula F, has good inhibition capability on RET kinase, and has good pharmacodynamic and pharmacokinetic performance and lower toxic and side effects.
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Paragraph 0227-0230; 0235-0236
(2021/07/01)
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- Preparation method of pyrazolo[1,5-a]pyridine derivative
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The invention discloses a preparation method of pyrazolo[1,5-a]pyridine derivatives, and belongs to the field of organic synthesis. The problems that an existing pyrazolo[1,5-a]pyridine structure synthesis method needs metal catalysis, the substrate range is limited, the total yield of multi-step reaction is low, stoichiometric additives, toxic oxidants and oxygen-free technologies are adopted, and reaction conditions are harsh are solved. The method comprises the steps: dissolving pyridinium salt, unsaturated alkene and 2,3-dichloro-5,6-dicyanobenzoquinone in an organic solvent, dropwise adding triethylamine to react, concentrating by a rotary evaporator to remove the solvent, and separating and purifying by silica gel column chromatography to obtain the pyrazolo[1,5-a]pyridine derivative.
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Paragraph 0037-0045
(2021/04/21)
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- RET inhibitor, pharmaceutical composition comprising same and application of RET inhibitor and pharmaceutical composition in medicines
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The invention belongs to the field of medicines, and relates to an RET inhibitor, a pharmaceutical composition comprising the same and application of the RET inhibitor and the pharmaceutical composition in medicines. Specifically, the invention relates to
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Paragraph 0253-0254
(2021/11/10)
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- SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS INHIBITORS OF FGFR TYROSINE KINASES
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Provided herein are compounds of the general Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which Ring A, Ring B, Ring C, R1, R2, L, Y, and W have the meanings given in the specification, which are inhibitors of FGFR1, FGFR2, FGFR3 and/or FGFR4 and are useful in the treatment and prevention of diseases which can be treated with an FGFR inhibitor, including diseases or disorders mediated by FGFR1, FGFR2, FGFR3 and/or FGFR4.
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Paragraph 001328
(2020/07/14)
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- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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Paragraph 00250
(2020/07/06)
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- RET kinase inhibitor intermediates and preparation method thereof
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The invention discloses RET kinase inhibitor intermediates and a preparation method thereof, and relates to the field of medicinal chemistry, wherein the method for synthesizing RET kinase inhibitorsrepresented by a formula (5a) and a formula (5b) comprises the steps: (a) carrying out a reaction of compounds represented by a formula (4a) and a formula (4b) with hydroxylamine sulfonic acid to formthe compounds represented by the formula (5a) and the formula (5b); and (b) carrying out a reaction of the compounds represented by a formula (3a) and a formula (3b) with phosphorus oxychloride to form compounds represented by the formula (4a) and the formula (4b); and (c) allowing compounds represented by a formula (2a) and a formula (2b) to form the compounds represented by the formula (3a) andformula (3b) under the action of an acid; and (d) after the reaction of the mixture of 3-bromo-5-methoxypyridine, hydroxylamine sulfonic acid and water is finished at the temperature of 70-100 DEG C,adding an alcoholic solution of alkali at room temperature, dropwise adding propiolate, and after the reaction is finished at room temperature, obtaining the compounds represented by the formula (2a)and the formula (2b), wherein R is methyl, ethyl, propyl or butyl.
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Paragraph 0033; 0046-0048
(2020/08/26)
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- FORMULATIONS COMPRISING 6-(2-HYDROXY-2-METHYLPROPOXY)-4-(6-(6-((6-METHOXYPYRIDIN-3-YL)METHYL)-3,6-DIAZAB ICYCLO[3.1.1]HEPTAN-3-YL)PYRIDIN-3-YL)PYRAZOLO[1,5-A]PYRIDINE-3-CARBONITRILE
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6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile, or a pharmaceutically acceptable salt, amorphous form, polymorph form, or pharmaceutical composition (including solid formulations or liquid formulations) thereof and the use thereof for treating diseases and disorders which can be treated with a RET kinase inhibitor, such as RET-associated diseases and disorders, e.g., proliferative disorders such as cancers, including hematological cancers and solid tumors, and gastrointestinal disorders such as IBS are disclosed.
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Page/Page column 309; 311; 312
(2019/05/06)
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- PROCESS FOR THE PREPARATION OF 6-(2-HYDROXY-2-METHYLPROPOXY)-4-(6-(6-((6-METHOXYPYRIDIN-3-YL)METHYL)-3,6-DIAZABICYCLO[3.1.1]HEPTAN-3-YL)PYRIDIN-3-YL)PYRAZOLO[1,5-A]PYRIDINE-3-CARBONITRILE
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In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.
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Paragraph 0285; 0287
(2019/04/25)
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- CRYSTALLINE FORMS
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Provided herein are compound of Formula I-IV and pharmaceutically acceptable salts thereof which exhibit rearranged during transfection (RET) kinase inhibition. In particular, provided herein are novel crystalline forms of 4-(6-(4-((6-methoxypyridin-3-yl)methyl)piperazin-1-yl)pyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula I), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula II), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-(6-methoxynicotinoyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula III), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(4-hydroxy-4-(pyridin-2-ylmethyl)piperidin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula IV), and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds, processes for making the compounds, and the use of the compounds in therapy. More particularly, the application relates to novel crystalline forms of Formula I-IV and pharmaceutically acceptable salts thereof useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.
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Paragraph 00599
(2019/05/02)
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- A 6 - bromo -4 - methoxy hydrogen - pyrazole [1, 5 - a] pyridine -3 - carbonitrile synthetic method (by machine translation)
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The invention belongs to the field of organic synthetic technology, provides a 6 - bromo - 4 - methoxy hydrogen - pyrazole [1, 5 - a] pyridine - 3 - carbonitrile synthetic method. The synthetic method comprises: (1) salt forming reaction: in order to 2, 4, 6 - trimethyl benzene sulfonyl hydroxylamine as raw materials in the organic solvent in the 1st with 3 - bromo - 5 - methoxy pyridine to obtain 2, 4, 6 - trimethyl benzenesulfonic acid 3 - bromo - 5 - methoxy pyridine amine salt; (2) the cyclization reaction: to 2, 4, 6 - trimethyl benzenesulfonic acid 3 - bromo - 5 - methoxy pyridine amine salt as raw materials in the presence of alkali of the 2nd organic solvent with 2 - chloro generates cyclization reaction to obtain the aroma of the 6 - bromo - 4 - methoxy hydrogen - pyrazole [1, 5 - a] pyridine - 3 - a nitrile. The method for synthesis of synthetic route is short, simple steps, greatly reduces the production cost, and is suitable for industrial production. (by machine translation)
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Paragraph 0025-0027
(2018/11/03)
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- SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
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Provided herein are compounds of the Formula I and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, X1, X2, X3, X4, Ring D, and E have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.
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Paragraph 00992; 00993; 00994
(2018/04/27)
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- SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
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Provided herein are compounds of the General Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.
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