Abstract: A package structure and a method of forming the same are provided. The package structure includes a first die, a second die, a first encapsulant, and a buffer layer. The first die and the second die are disposed side by side. The first encapsulant encapsulates the first die and the second die. The second die includes a die stack encapsulated by a second encapsulant encapsulating a die stack. The buffer layer is disposed between the first encapsulant and the second encapsulant and covers at least a sidewall of the second die and disposed between the first encapsulant and the second encapsulant. The buffer layer has a Young's modulus less than a Young's modulus of the first encapsulant and a Young's modulus of the second encapsulant.

Abstract: Provided herein are improved processes and methods for preparing osimertinib or a salt thereof, in particular osimertinib mesylate. The improved process removes the necessity of isolating the unstable aniline intermediate of formula (III) and enables the direct coupling to form the amide product of formula (II): The present invention is suitable for a large-scale production, avoiding the isolation of unstable intermediate, thereby providing osimertinib or a mesylate salt thereof in both high yields and high purity.

Abstract: A one-pot process for preparing cedazuridine of formula (I), comprising: subjecting a compound of formula (M3) to deprotection and then epimerization in a reactor in the presence of a catalyst to obtain a reaction mixture comprising cedazuridine, wherein R on the compound of formula (M3) is independently selected from the group consisting of Ac (acetyl), Bz (benzoyl), p-nitrobenzoyl and OtBu (tert-butyloxycarbonyl), and the deprotection and epimerization are conducted in the same reactor without isolating after the deprotection and before the epimerization; and isolating cedazuridine from the reaction mixture.

Abstract: In certain aspects, the invention provides crystalline forms of ivacaftor N-(2,4-di-tert-butyl-phenyl-5-hydroxy-phenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide. In related aspects, the invention provides a process for preparing any one of crystalline forms S2, S3, S4 and S5 of ivacaftor. The process includes: forming a solution including crude ivacaftor and a solvent; adding an anti-solvent to the solution to form slurry including a precipitate; isolating the precipitate; and drying the precipitate to provide crystalline form S2, S3, S4, or S5 of ivacaftor.

Abstract: Provided herein are improved processes and methods for preparing osimertinib or a salt thereof, in particular osimertinib mesylate. The improved process removes the necessity of isolating the unstable aniline intermediate of formula (III) and enables the direct coupling to form the amide product of formula (II): The present invention is suitable for a large-scale production, avoiding the isolation of unstable intermediate, thereby providing osimertinib or a mesylate salt thereof in both high yields and high purity.

Abstract: In certain aspects, the invention provides crystalline forms of ivacaftor N-(2,4-di-tert-butyl-phenyl-5-hydroxy-phenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide. In related aspects, the invention provides a process for preparing any one of crystalline forms S2, S3, S4 and S5 of ivacaftor. The process includes: forming a solution including crude ivacaftor and a solvent; adding an anti-solvent to the solution to form slurry including a precipitate; isolating the precipitate; and drying the precipitate to provide crystalline form S2, S3, S4, or S5 of ivacaftor.

Abstract: In certain aspects, the invention provides a novel crystalline form of olaparib (4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one). In related aspects, the invention provides a processe for preparing the novel crystalline form of olaparib. The process includes forming a solution comprising crude olaparib and an organic solvent; adding the solution to an anti-solvent to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form III of olaparib.

Abstract: Crystalline form S1 of lifitegrast characterized by a powder X-ray diffraction pattern with peaks at about 10.7±0.2, 16.2±0.2, 19.9±0.2, 22.1±0.2, 24.7±0.2, and 25.9±0.2 degrees two-theta, crystalline form S2 of lifitegrast characterized by a powder X-ray diffraction pattern with peaks at about 16.4±0.2, 24.9±0.2, and 26.2±0.2 degrees two-theta, and processes of making thereof are provided.

Abstract: Crystalline form S1 of lifitegrast characterized by a powder X-ray diffraction pattern with peaks at about 10.7±0.2, 16.2±0.2, 19.9±0.2, 22.1±0.2, 24.7±0.2, and 25.9±0.2 degrees two-theta, crystalline form S2 of lifitegrast characterized by a powder X-ray diffraction pattern with peaks at about 16.4±0.2, 24.9±0.2, and 26.2±0.2 degrees two-theta, and processes of making thereof are provided.

Abstract: In certain aspects, the invention provides crystalline forms of olaparib (4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one). In related aspects, the invention provides processes for preparing the crystalline forms of olaparib. The processes include: forming a solution comprising crude olaparib and an organic solvent; adding an anti-solvent to the solution to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form I of olaparib or a crystalline form II of olaparib.

Abstract: In certain aspects, the invention provides crystalline forms of olaparib (4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one). In related aspects, the invention provides processes for preparing the crystalline forms of olaparib. The processes include: forming a solution comprising crude olaparib and an organic solvent; adding an anti-solvent to the solution to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form I of olaparib or a crystalline form II of olaparib.

Abstract: The present invention provides novel crystalline forms of apremilast hemitoluene solvate, apremilast hydrate, and apremilast anhydrate and an amorphous form of apremilast, and processes for the preparation of these forms.

Abstract: A process for preparing an amorphous form of idelalisib comprises: (a) forming a first solution of idelalisib in a solvent; (b) adding the first solution obtained in step (a) into water to form a second solution; (c) optionally cooling the second solution obtained in step (b) and; (d) isolating the optionally cooled second solution from step (c) to provide the amorphous form of idelalisib. Mild reaction conditions are used in this process. The amorphous form of idelalisib prepared by this process is stable and does not transfer to other crystalline forms easily. This process is suitable for large scale manufacture of idelalisib at a high yield.

Abstract: In certain aspects, the invention provides crystalline forms of olaparib (4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one). In related aspects, the invention provides processes for preparing the crystalline forms of olaparib. The processes include: forming a solution comprising crude olaparib and an organic solvent; adding an anti-solvent to the solution to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form I of olaparib or a crystalline form II of olaparib.

Abstract: The present invention provides novel crystalline forms of apremilast hemitoluene solvate, apremilast hydrate, and apremilast anhydrate and an amorphous form of apremilast, and processes for the preparation of these forms.

Abstract: A process of making entecavir comprising converting a compound of formula (M5) to entecavir, wherein the two PGs on the formula (M5) are taken together to form an optionally substituted six- or seven-member cyclic ring.

Abstract: Novel crystalline forms of topotecan hydrochloride and processes of making the same are disclosed.

Abstract: A process of making entecavir comprising converting a compound of formula (M5) to entecavir, wherein the two PGs on the formula (M5) are taken together to form an optionally substituted six- or seven-member cyclic ring.

Abstract: A process of making topotecan or a pharmaceutically acceptable salt thereof comprising reacting an iminium salt with 10-hydroxy-camptothecin.

Abstract: A process for making a capecitabine or its derivative comprising (a) reacting a compound of the formula (II): wherein each of R1 and R2 independently represents a hydroxyl protecting group, with an acylating agent of formula (III): X—C(?O)—R3, wherein X is an acyl activating group in an organic solvent to produce an acylated compound; (b) deprotecting the acylated compound to obtain the compound of formula (I); and (c) purifying the compound of formula (I) with a solvent.