Abstract: 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.

Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.

Abstract: The present invention provides processes and key intermediates for the synthesis of (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoro-propane-2-yl)-1H-pyrazole-4-carboxamide:

Abstract: 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.

Abstract: 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.

Abstract: Process for preparing (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide (formula I) or a salt thereof by reacting phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate or a similar derivative (formula 13) with (S)-pyrrolidin-3-ol (formula 14). Process for preparing phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate (formula 13) or a similar derivative by reduction of (R)-5-(2-(2,5-difluorophenyl) pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine (formula 11) to (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (formula 12). Process for preparing (R)-2-(2,5-difluorophenyl)pyrrolidine(R)-2-hydroxysuccinate (formula 10) by treating (R)—N—((R)-1-(2,5-difluorophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (formula 19) with an acid and a reducing agent.

Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.

Abstract: A spray-dried dispersions and pharmaceutical composition of (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the spray-dried dispersion and pharmaceutical composition in the treatment of cancer and autoimmune and inflammatory diseases are disclosed. Also provided are crystalline forms of (S)-5-amino-3-(4-((5-fluoro-2-methoxy-benzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide also useful in the treatment of cancer and autoimmune and inflammatory diseases.

Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.

Abstract: In some embodiments, provided herein are processes for preparing a compound of Formula C or a salt thereof, as disclosed herein. In some embodiments, provided herein is a compound of Formula I or a pharmaceutically acceptable salt, solvate or hydrate thereof. In some embodiments, provided herein is a solid form of the compound, such as a crystalline form of the compound crystalline Form I.

Abstract: 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.

Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.

Abstract: 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.

Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.

Abstract: In some embodiments, provided herein are processes for preparing a compound of Formula C or a salt thereof, as disclosed herein. In some embodiments, provided herein is a compound of Formula I or a pharmaceutically acceptable salt, solvate or hydrate thereof. In some embodiments, provided herein is a solid form of the compound, such as a crystalline form of the compound crystalline Form I.

Abstract: 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.

Abstract: The present application in some embodiments provides a pharmaceutical composition comprising: and a compounding agent. Further provided herein are methods of making and methods of using the pharmaceutical compositions, for example, in the treatment of cancer.

Abstract: Process for preparing (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide (formula I) or a salt thereof by reacting phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate or a similar derivative (formula 13) with (S)-pyrrolidin-3-ol (formula 14). Process for preparing phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate (formula 13) or a similar derivative by reduction of (R)-5-(2-(2,5-difluorophenyl) pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine (formula 11) to (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (formula 12). Process for preparing (R)-2-(2,5-difluorophenyl)pyrrolidine(R)-2-hydroxysuccinate (formula 10) by treating (R)—N—((R)-1-(2,5-difluorophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (formula 19) with an acid and a reducing agent.

Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.

Abstract: Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in the treatment of autoimmunity, inflammation allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer and immunodeficiency.