Abstract: A manufacturing process to a bis-mesylate salt 1b of the pan-RAF inhibitor 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide. The process features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective PtN/C-catalyzed nitro group reduction to access penultimate intermediate 7. The final amide coupling of 7 and 2 was accomplished by a mild and safe protocol employing N,N,N?,N?-tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the coupling reagent, to produce a 1:1 adduct of the freebase and THF. The adduct afforded compound 1b with excellent yield, purity, and form stability on a multikilogram production scale after reaction with MsOH and recrystallization. The methods are able to produce a compound having upwards of 95% purity.

Abstract: The invention relates to a container for holding and storing liquids and viscous materials, in particular cryogenic fluids, comprising a jacket (12), which defines the interior (14) of the container (10) having a chamber (16), said container (10) being constituted of at least two container structures (20, 20?, 20?) and each of said at least two container structures (20, 20?, 20?) being formed as one piece from a blank (32) and having a dome portion (22), a branching portion (24), which is contiguous to the dome portion (22), and two cylinder portions (26, 28; 26?, 28?), which are contiguous to the branching portion (24), and the mutually facing container structures (20, 20; 20?, 20?) which are adjacent to each other being joined together.

Abstract: The invention relates to a container for holding and storing liquids and viscous materials, in particular cryogenic fluids, comprising a jacket (12), which defines the interior (14) of the container (10) having a chamber (16), said container (10) being constituted of at least two container structures (20, 20?, 20?) and each of said at least two container structures (20, 20?, 20?) being formed as one piece from a blank (32) and having a dome portion (22), a branching portion (24), which is contiguous to the dome portion (22), and two cylinder portions (26, 28; 26?, 28?), which are contiguous to the branching portion (24), and the mutually facing container structures (20, 20; 20?, 20?) which are adjacent to each other being joined together.