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Journal of Organic Chemistry | 2014

Synthesis of the 6-Azaindole Containing HIV-1 Attachment Inhibitor Pro-Drug, BMS-663068

Ke Chen; Christina Risatti; Michael Bultman; Maxime Soumeillant; Jim Simpson; Bin Zheng; Dayne Fanfair; Michelle Mahoney; Boguslaw Mudryk; Richard J. Fox; Yi Hsaio; Saravanababu Murugesan; David A. Conlon; Frederic G. Buono; Martin D. Eastgate

The development of a short and efficient synthesis of a complex 6-azaindole, BMS-663068, is described. Construction of the 6-azaindole core is quickly accomplished starting from a simple pyrrole, via a regioselective Friedel-Crafts acylation, Pictet-Spengler cyclization, and a radical-mediated aromatization. The synthesis leverages an unusual heterocyclic N-oxide α-bromination to functionalize a critical C-H bond, enabling a highly regioselective copper-mediated Ullmann-Goldberg-Buchwald coupling to install a challenging triazole substituent. This strategy resulted in an efficient 11 step linear synthesis of this complex clinical candidate.


Tetrahedron Letters | 1995

4-Hydroxy-2-methyl-3(2H)-isothiazolone-1,1-dioxide as protecting group of 4-(N-methylaminosulfonyl)methylphenylhydrazine during Fischer indole synthesis

Philippe Remuzon; Christian Dussy; Jean-Pierre Jacquet; Maxime Soumeillant; Daniel Bouzard

Abstract Protection of the benzylic position of 4-methylaminosulfonylmethylphenyl hydrazine 6 with a 4-hydroxy-2-methyl-3(2 H )-isothiazolone-1,1-dioxide group allowed the preparation of indole 3 without formation of side-product.


Tetrahedron | 1997

Synthesis of chiral α-substituted N-[((2S)-2-hydroxy-2-phenyl)-ethyl]-2-phenylglycine derivatives by diastereocontrolled alkylation of (6 R)-2,3,5,6-tetrahydro-3,6-diaryl-N-[(2′R)-(2′-methyl)phenyl-methyl]-4H-1,4-oxazin-2-ones

Philippe Remuzon; Maxime Soumeillant; Christian Dussy; Daniel Bouzard

Abstract The synthesis of α-substituted N-[((2S)-2-hydroxy-2-phenyl)-ethyl]-2-phenylglycine derivatives is reported. The key step of the sequence is the highly diastereoselective alkylation of (6R)-2,3,5,6-tetrahydro-3,6-diaryl-N-[(2′R)-(2′-methyl)phenylmethyl]-4H-1,4-oxazin-2-ones after deprotonation with t-BuOK. Opening of the resulting oxazinone with ethanolic KOH, followed by hydrogenolysis of the corresponding N-[(2R)-(2-methyl)phenylmethyl] compound to furnish the expected 2-phenylglycine derivative, is also described.


Journal of Organic Chemistry | 2017

Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy

Adrian Ortiz; Maxime Soumeillant; Scott A. Savage; Neil A. Strotman; Matthew W. Haley; Tamas Benkovics; Jeffrey S. Nye; Zhongmin Xu; Yichen Tan; Sloan Ayers; Qi Gao; Susanne Kiau

A concise and scalable second generation synthesis of HIV maturation inhibitor BMS-955176 is described. The synthesis is framed by an oxidation strategy highlighted by a CuI mediated aerobic oxidation of betulin, a highly selective PIFA mediated dehydrogenation of an oxime, and a subsequent Lossen rearrangement which occurs through a unique reaction mechanism for the installation of the C17 amino functionality. The synthetic route proceeds in 7 steps with 47% overall yield and begins from the abundant and inexpensive natural product betulin.


Journal of Organic Chemistry | 2018

Effects of Multiple Catalyst Deactivation Pathways and Continuous Ligand Recycling on the Kinetics of Pd-Catalyzed C–N Coupling Reactions

Neil A. Strotman; Maxime Soumeillant; Keming Zhu; Chester E. Markwalter; Carolyn S. Wei; Yi Hsiao; Martin D. Eastgate

Unusual Pd deactivation and inhibition pathways were observed in a C-N coupling system. Irreversible catalyst deactivation involved C-H insertion of Pd into BippyPhos leading to an off-cycle palladaphosphacyclobutene. Product inhibition led to deactivated Pd but released ligand in the process, allowing it to react with additional Pd precursor to re-enter the catalytic cycle. In situ recycling of the ligand allowed for an input L/Pd ratio of ≪1 with no impact on reaction kinetics.


Organic Letters | 2007

Mild and General Methods for the Palladium-Catalyzed Cyanation of Aryl and Heteroaryl Chlorides

Adam Littke; Maxime Soumeillant; Robert F. Kaltenbach; Robert J. Cherney; and Christine M. Tarby; Susanne Kiau


Advanced Synthesis & Catalysis | 2008

Rhodium-Catalyzed Cyclopropanation of Alkenes with Dimethyl Diazomalonate

Francisco González-Bobes; Michaël D. B. Fenster; Susanne Kiau; Laxma Kolla; Sergei V. Kolotuchin; Maxime Soumeillant


Organic Process Research & Development | 2001

Chemical and Enzymatic Resolution of (R,S)-N-(tert-Butoxycarbonyl)-3-hydroxymethylpiperidine

Animesh Goswami; Jeffrey M. Howell; Edward Y. Hua; K. David Mirfakhrae; Maxime Soumeillant; Shankar Swaminathan; Xinhua Qian; Fernando Quiroz; Truc Chi Vu; Xuebao Wang; Bin Zheng; and David R. Kronenthal; Ramesh N. Patel


Organic Process Research & Development | 2008

Kilogram Synthesis of a Selective Serotonin Reuptake Inhibitor

Robert Anthes; Osagie Bello; Serge Benoit; Chien-Kuang Chen; Elisabeth Corbett; Richard M. Corbett; Albert J. DelMonte; Stephane Gingras; Robert C. Livingston; Justin Sausker; Maxime Soumeillant


Organic Process Research & Development | 2002

A Practical Synthesis of l-Valyl-pyrrolidine-(2R)-boronic Acid: Efficient Recycling of the Costly Chiral Auxiliary (+)-Pinanediol

Frank Gibson; Ambarish K. Singh; Maxime Soumeillant; Percy S. Manchand; Michael Humora; David R. Kronenthal

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