1207557-36-5Relevant articles and documents
RET kinase inhibitor intermediates and preparation method thereof
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Paragraph 0033-0038, (2020/08/26)
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.
CRYSTALLINE FORMS
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Paragraph 00591-00593; 00619; 00620, (2019/05/02)
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.
SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
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Paragraph 00805; 00807; 00808, (2018/04/27)
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.
