66616-26-0Relevant academic research and scientific papers
Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-xL Antagonist. 2. Manufacture of the 1,3-Diamine Moiety and Improvement of the Final Coupling Reaction
Hardouin, Christophe,Baillard, Sandrine,Barière, Fran?ois,Craquelin, Anthony,Grandjean, Mathieu,Janvier, Solenn,Le Roux, Stéphane,Penloup, Christine,Russo, Olivier
, p. 670 - 685 (2019/12/24)
This paper describes the synthesis of kilogram quantities of the sulfonamide moiety 3 involved in a coupling reaction with acid moiety 2 to provide batches of drug candidate 1 for preclinical studies and first-in-human clinical trials. A first approach relying on a chiral separation furnished the desired enantiomer of 1,3-diamine 20, precursor of sulfonamide 3. An enantiomeric synthesis of 20 using the Ellman's chiral auxiliary coupled with an aza-Reformatsky reaction to control the stereochemistry is also discussed. Coupling conditions of the final step involving EDCI to provide 1 under a cGMP process are detailed. An alternative approach using N-(1-methanesulfonyl)benzotriazole is also presented.
Process for preparing sulfonamide compounds
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Paragraph 0494; 0545-0548, (2020/07/24)
The invention relates to a process for preparing sulfonamide compounds. The sulfonamide compound is an inhibitor of Bcl-2/Bcl-xL and is prepared from a compound (3R)-1-(3-(4-(4-(4-(3-(2-(4-chlorphenyl)-1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrole-3-yl
PROCESS FOR PREPARING SULFONAMIDE COMPOUNDS
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Page/Page column 91-92, (2020/09/03)
Provided are a process for preparing a sulfonamide compound which is an inhibitor of Bcl-2/Bcl-xL, including the compound (3R) -1- (3- (4- (4- (4- (3- (2- (4-chlorophenyl) -1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl) -5-fluorophenyl) piperazine
2-(phenylthio)ethylidene derivatives as anti-Trypanosoma cruzi compounds: Structural design, synthesis and antiparasitic activity
Cardoso, Marcos Veríssimo de Oliveira,de Oliveira Filho, Gevanio Bezerra,de Siqueira, Lucianna Rabelo Pessoa,Espíndola, José Wanderlan Pontes,Silva, Elany Barbosa da,Mendes, Andresa Pereira de Oliveira,Pereira, Valéria Rêgo Alves,de Castro, Maria Carolina Accioly Brelaz,Ferreira, Rafaela Salgado,Villela, Filipe Silva,Costa, Francielly Morais Rodrigues da,Meira, Cássio Santana,Moreira, Diogo Rodrigo Magalh?es,Soares, Milena Botelho Pereira,Leite, Ana Cristina Lima
, p. 191 - 203 (2019/07/16)
Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi. The current chemotherapy is based on benznidazole, and, in some countries, Nifurtimox, which is effective in the acute phase of the disease, but its efficacy in the chronic p
Dioxazolones as masked ester surrogates in the Pd(ii)-catalyzed direct C-H arylation of 6,5-fused heterocycles
Saxena, Paridhi,Maida, Neha,Kapur, Manmohan
supporting information, p. 11187 - 11190 (2019/09/30)
A simple and effective Pd(ii)-catalyzed regioselective C(2)-H arylation of 6,5-fused heterocycles with dioxazolones as a masked ester surrogate under mild conditions is reported. The significance of the arylation is highlighted by the new reactivity demonstrated in dioxazolones via proximal C-H activation of the cyclic carbonate of the hydroxamic acid functionality under protic conditions.
Scalable asymmetric synthesis of a key fragment of Bcl-2/Bcl-xLinhibitors
Laclef, Sylvain,Taillier, Catherine,Penloup, Christine,Viger, Aurélie,Brière, Jean-Fran?ois,Hardouin, Christophe,Levacher, Vincent
, p. 39817 - 39821 (2015/02/02)
The asymmetric synthesis of a 1,3-diamine building block for the elaboration of Bcl-2 and Bcl-xLprotein inhibitors is described through two key steps: (1) a highly diastereoselective aza-Reformatsky reaction, and (2) a chemoselective amination under Mitsunobu conditions. This synthetic sequence was also demonstrated to be successfully amenable to a large-scale synthesis. This journal is
Sulfur-directed regioselective radical cyclization leading to β-lactams: Formal synthesis of (±)-PS-5 and (+)-thienamycin
Ishibashi,Kameoka,Iriyama,Kodama,Sato,Ikeda
, p. 1276 - 1284 (2007/10/02)
A new method for the synthesis of β-lactams by tributyltin hydride (Bu3SnH)-mediated radical cyclizations of N-ethenyl-α-bromo amides bearing sulfur-substituent(s) at the terminus of the N-vinylic bond is described. N-[2-(Phenylthio)ethenyl]-α-
Enantioselective Synthesis of 2-Sulfenylated Aldehydes: Alkylation of Sulfenylated Acetaldehyde SAMP-Hydrazones
Enders, Dieter,Schaefer, Thomas,Piva, Olivier,Zamponi, Andrea
, p. 3349 - 3362 (2007/10/02)
A practical and efficient enantioselective synthesis of 2-sulfenylated aldehydes (S)-6 is described, based on the α-alkylation of sulfenylated acetaldehyde SAMP hydrazones (S)-4, easily prepared from bromoacetaldehyde diethylacetal 1, thiols and (S)-1-amino-2-methoxymethyl-pyrrolidine (SAMP).A chemoselective oxidative cleavage of the intermediate SAMP hydrazones (S,S)-5 with ozone gives rise to the title compounds (S)-6 in good overall yields and high enantiomeric excess of up to 97percent.
Generation of Sulfur-Functionalized Nitrile Oxide, (Phenylthio)-acetonitrile Oxide, and Synthetic Applications
Kanemasa, Shuji,Norisue, Yasumasa,Suga, Hiroyuki,Tsuge, Otohiko
, p. 3973 - 3982 (2007/10/02)
The first generation of a new sulfur-functionalized nitrile oxide 1,3-dipole, (phenylthio)acetonitrile oxide, is presented.Its cycloadditions to a variety of olefins and acetylenes lead to 3-(phenylthiomethyl)-2-isoxazolines and -oxazoles, the formers bei
