Abstract: Provided herein is a process for preparing compound A comprising (a) admixing 2-isopropyl-4-methylpyridin-3-amine (Compound B), or a salt thereof, a first base, and a reactive compound comprising phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanato-2-isopropyl-4-methylpyridine (Compound C); (b) admixing Compound C and 2,6-dichloro-5-fluoronicotinamide (Compound D) to form 2,6-dichloro-5-fluoro-N-((2-isopropyl-4-methylpyridin-3-yl)carbamoyl)nicotinamide (Compound E); and (c) admixing Compound E and a second base to form a product mixture comprising Compound A and the second base.

Abstract: Disclosed herein are salt and solvate forms of (4S,7aR,9aR,10R,11E,14S,15R)-6?-chloro-10-methoxy-14,15-dimethyl-10-{[(9aR)-octahydro-2H-pyrido[1,2-a]pyrazin-2-yl]methyl}-3?,4?,7a,8,9,9a,10,13,14,15-decahydro-2?H,3H,5H-spiro[1,19-etheno-16,16-cyclobuta[i][1,4]oxazepino[3,4-f][1,2,7]thiadlazacyclohexadecine-4,1 naphthalene]-16,16,18 (7H,17H)-trione (AMG 397): (AMG 397), such as crystalline salt and solvate forms thereof. Also disclosed are methods of making the salt and solvate forms, and methods of treating diseases and disorders with the salt and solvate forms.

Abstract: Disclosed herein are crystalline forms of (4S,7aR,9aR,10R,11E,14S,15R)-6?-chloro-10-methoxy-14,15-dimethyl-10-{[(9aR)-octahydro-2H-pyrido[1,2-a]pyrazin-2-yl]methyl}-3?,4?,7a,8,9,9a,10,13,14,15-decahydro-2?H,3H,5H-spiro[1,19-etheno-1616-cyclobuta[i] [1,4]oxazepino[3,4-f][1,2,7]thiadiazacyclohexadecine-4,1?-naphthalene]-16,16,18(7H,17H)-trione (AMG 397): (AMG 397), hydrates, and solvates thereof. Also disclosed are methods of making the crystalline forms, and methods of treating diseases and disorders with the crystalline forms.

Abstract: The present invention relates to methods for separating enantiomers of 5-phenyl and 5-naphthyl substituted 4-(aminomethyl)-6-(1-methyl-1H-pyrazol-4-yl)phthalazin-1(2H)-ones using N-Boc-L-phenylalanine, N-Boc-D-phenylalanine, and similar chiral acids.

Abstract: The present invention relates to improved synthetic routes of synthesizing adagrasib. The invention also provides intermediates used in the provided synthetic routes.

Abstract: Disclosed herein are crystalline forms of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile free base, pharmaceutically acceptable compositions comprising these crystalline forms, and methods for using these crystalline forms.

Abstract: Provided herein is a process for preparing compound A comprising (a) admixing 2-isopropyl-4-methylpyridin-3-amine (Compound B), or a salt thereof, a first base, and a reactive compound comprising phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanato-2-isopropyl-4-methylpyridine (Compound C); (b) admixing Compound C and 2,6-dichloro-5-fluoronicotinamide (Compound D) to form 2,6-dichloro-5-fluoro-N-((2-isopropyl-4-methylpyridin-3-yl)carbamoyl)nicotinamide (Compound E); and (c) admixing Compound E and a second base to form a product mixture comprising Compound A and the second base. Also provided herein is a process for synthesizing AMG 510 comprising using Compound A prepared according to the disclosed processes [Insert Structure] (Compound A).

Abstract: Disclosed herein is an improved process for the synthesis of compound (A): (A), or a salt or solvate thereof via methylation of compound (B): (B), or a salt or solvate thereof, a crystalline hydrate of compound A, and pharmaceutical formulations comprising a crystalline hydrate of compound (A).

Abstract: The present disclosure relates to a method of capping, reducing, and oxidizing cys-mAbs in order to provide homogenous material for subsequent conjugation reactions. The present method demonstrates robust ways to manufacture conjugates of cysteine-engineered antibodies that offer high yield and consistent product quality.