1545932-86-2

Upstream product

• 76272-34-9 8-Benzyl-1αH,5αH-nortropan-3-one Oxime 
• 132259-54-2 exo-(8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl)-carbamic acid tert-butyl ester 
• 376348-67-3 exo-N-(8-benzyl-8-azabicyclo[3.2.1]oct-3-yl)-2-methylpropanamide 
• 76272-36-1 8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl-amine 
• 423165-13-3 exo-8-benzyl-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane 
• 104-15-4 toluene-4-sulfonic acid 
• 28957-72-4 N-benzylnortropinone 

Downstream Products

• 376348-70-8 tert-butyl (1S)-3-[3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-exo-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropylcarbamate 
• 1519003-75-8 C₃₃H₅₂N₈O 
• 1519003-85-0 C₃₀H₄₆N₈O₄ 
• 1519003-78-1 C₅₅H₈₁N₉O₈ 
• 376348-65-1 4,4-difluoro-N-[(1S)-3-[(1R,5S)-3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxamide 
• 376348-65-1 maraviroc 
• 376348-71-9 (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine 

Relevant academic research and scientific papers

Process research and scale-up of a commercialisable route to maraviroc (UK-427,857), a CCR-5 receptor antagonist

A six-step synthetic route to the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1) has been developed and demonstrated at scale in a pilot plant. The route has supported four Pilot-Plant campaigns and has produced multikilogram quantities of 1. Continued development of the synthetic route has resulted in a robust process with improved throughput compared to that of the original synthesis (Haycock-Lewandowski, S. J.; Mawby, N. J.; Wilder, A.; Ahman, J. Org. Process Res. Dev. 2008, 12, 1094-1103).

Asymmetric Mannich Reaction and Construction of Axially Chiral Sulfone-Containing Styrenes in One Pot from α-Amido Sulfones Based on the Waste-Reuse Strategy

A simultaneous asymmetric Mannich reaction and the construction of axially chiral sulfone-containing styrenes in one pot from α-amido sulfones based on the waste-reuse strategy was demonstrated. A series of chiral β-amino diesters and axially chiral sulfone-containing styrenes with various functional groups were synthesized in good to excellent yields and enantioselectivities under mild conditions. In addition, this protocol has been successfully applied to synthesize the anti-HIV drug Maraviroc and chiral trichloro derivatives.

Preparation and activities of macromolecule conjugates of the CCR5 antagonist maraviroc

CCR5 antagonists are among the most advanced approaches in HIV therapy and may also be relevant to treatment of graft-versus-host disease and Staphylococcus aureus infection. To expand the potential of the only approved CCR5 antagonist, Maraviroc, we studied derivatives that would enable functional linkage of Maraviroc to long-lived carriers. Through targeted synthesis, we discovered an effective linkage site on Maraviroc and demonstrate the potential of these derivatives to prepare potent chemically programmed antibodies and PEGylated derivatives. The resulting compounds effectively neutralized a variety of HIV-1 isolates. Both chemically programmed antibody and PEGylation approaches extend the neutralization activity of serum circulating Maraviroc. Derivation of a successful conjugation strategy for Maraviroc should further enable its use in chemically programmed vaccines, novel bispecific antibodies, and topical microbicides.

Asymmetric synthesis of maraviroc (UK-427,857)

The asymmetric synthesis of Maraviroc (UK-427,857), a chemochine receptor 5 (CCR-5) receptor antagonist, based on an expeditious organocatalytic enantioselective assembly of the chiral βamino aldehyde key fragment is presented. The reactions were performed on a gram-scale and allow for the rapid construction of new Maraviroc analogues.

Development of a bulk enabling route to maraviroc (UK-427,857), a CCR-5 receptor antagonist

A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1), is presented. Synthesis of the three key fragments, β-amino ester 3,4,4-difluorohexanecarboxylic acid (2), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation, and final scale-up of the developed route to 1.