173334-57-1Relevant articles and documents
End-to-end continuous manufacturing of pharmaceuticals: Integrated synthesis, purification, and final dosage formation
Mascia, Salvatore,Heider, Patrick L.,Zhang, Haitao,Lakerveld, Richard,Benyahia, Brahim,Barton, Paul I.,Braatz, Richard D.,Cooney, Charles L.,Evans, James M. B.,Jamison, Timothy F.,Jensen, Klavs F.,Myerson, Allan S.,Trout, Bernhardt L.
, p. 12359 - 12363 (2013)
A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug product in one integrated system. Copyright
Development of a multi-step synthesis and workup sequence for an integrated, continuous manufacturing process of a pharmaceutical
Heider, Patrick L.,Born, Stephen C.,Basak, Soubir,Benyahia, Brahim,Lakerveld, Richard,Zhang, Haitao,Hogan, Rachael,Buchbinder, Louis,Wolfe, Aaron,Mascia, Salvatore,Evans, James M. B.,Jamison, Timothy F.,Jensen, Klavs F.
, p. 402 - 409 (2014)
The development and operation of the synthesis and workup steps of a fully integrated, continuous manufacturing plant for synthesizing aliskiren, a small molecule pharmaceutical, are presented. The plant started with advanced intermediates, two synthetic steps away from the final active pharmaceutical ingredient, and ended with finished tablets. The entire process was run on several occasions, with the data presented herein corresponding to a 240 h run at a nominal throughput of 41 g h-1 of aliskiren. The first reaction was performed solvent-free in a molten condition at a high temperature, achieving high yields (90%) and avoiding solid handling and a long residence time (due to higher concentrations compared to dilute conditions when run at lower temperatures in a solvent). The resulting stream was worked-up inline using liquid-liquid extraction with membrane-based separators that were scaled-up from microfluidic designs. The second reaction involved a Boc deprotection, using aqueous HCl that was rapidly quenched with aqueous NaOH using an inline pH measurement to control NaOH addition. The reaction maintained high yields (90-95%) under closed-loop control despite process disturbances.
Preparation method of aliskiren
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, (2017/02/02)
The invention discloses a preparation method of aliskiren. Aliskiren is prepared from (R)-t-butylsulfenamide and a compound VIII. The chiral induction effect of the (R)-t-butylsulfenamide is used to construct a required second chiral center and solve the problem of column chromatographic separation needed in the construction of a second chiral center, a third chiral center and a fourth chiral center. The preparation method of aliskiren has the advantages of simple operation, high yield, low cost, high device utilization rate, and suitableness for industrial production.
PROCESS FOR THE PREPARATION OF ALISKIREN
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, (2014/09/29)
The present invention provides a novel process and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren, or a salt thereof, preferably Aliskiren hemifumarate.
