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
Removal of heavy metals from organic reaction mixtures: Preparation and application of functionalized resins
Barbaras, Damien,Brozio, Joerg,Johannsen, Ib,Allmendinger, Thomas
, p. 1068 - 1079 (2009)
Using a toolbox, sulfur and amine ligands are attached to a variety of hydrophobic and hydrophilic resins, and the combinations were tested for the removal of heavy metals from a number of products, prepared by metal-catalyzed reactions. As a result, cheap combinations of silica resins and simple polyamines proved to be among the most effective metal scavengers particularly in apolar solvents such as cyclohexane. Expensive cyclic polyamines are not suitable, owing to kinetic retardation of complexation. Functionalized PEGbased polymers, originally designed for solid phase synthesis, show promising performance as metal scavengers. The results are discussed and compared to alternative approaches for purification such as salt-formation and chemical downstream transformation.
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.
Convergent Synthesis of the Renin Inhibitor Aliskiren Based on C5-C6 Disconnection and CO2H-NH2 Equivalence
Cini, Elena,Banfi, Luca,Barreca, Giuseppe,Carcone, Luca,Malpezzi, Luciana,Manetti, Fabrizio,Marras, Giovanni,Rasparini, Marcello,Riva, Renata,Roseblade, Stephen,Russo, Adele,Taddei, Maurizio,Vitale, Romina,Zanotti-Gerosa, Antonio
, p. 270 - 283 (2016/03/04)
A novel synthesis of the renin inhibitor aliskiren based on an unprecedented disconnection between C5 and C6 was developed, in which the C5 carbon acts as a nucleophile and the amino group is introduced by a Curtius rearrangement, which follows a simultaneous stereocontrolled generation of the C4 and C5 stereogenic centers by an asymmetric hydrogenation. Operational simplicity, step economy, and a good overall yield makes this synthesis amenable to manufacture on scale.
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 PREPARING 8-ARYLOCTANOIC ACIDS
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Page/Page column 32; 33, (2015/02/02)
The present invention relates to a process for preparing aliskiren and, more particularly, to an improved method for synthesizing a β-amino alcohol or a lactone analog thereof via the corresponding nitro derivatives of formula (Ia) or (Ib) these intermediates being used in the preparation of aliskiren.
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.
PROCESS FOR THE PREPARATION OF ALISKIREN
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, (2013/10/21)
The present invention relates to an improved process for the preparation of Aliskiren and its pharmaceutically acceptable salts comprising reducing the compound of Formula-Z in presence of catalyst and ammonia. The present invention further relates to Aliskiren hemifumarate having diastereomeric impurity less than 0.2%.(F) H3C CH3 NH2 H3C 0 H3C CH3 Formula-Z
PROCESS FOR THE PREPARATION OF ALISKIREN
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, (2013/05/21)
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.
METHOD FOR PREPARING ALISKIREN AND INTERMEDIATE THEREOF
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, (2013/03/26)
A method for preparing Aliskiren and intermediate thereof, which comprises the following steps: reacting 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene with magnesium isopropyl chloride and n-BuLi to obtain the compound of formula XXII; reacting the product of methylsulfonylation of the compound of formula XIX with anhydrous LiBr to obtain the compound of formula XXI; obtaining the intermediate of Aliskiren shown as formula XV by reacting the compound of formula XXII with the compound of formula XXI in an ether as the solvent and in the presence of a catalyst containing iron; then reacting the compound of formula XV with the compound of formula VII to obtain the compound of formula XXIII, following removing R1 from the amino group and obtaining Aliskiren shown as formula I.
