70869-86-2Relevant academic research and scientific papers
DIVERSITY-ORIENTED SYNTHESIS OF N,N,O-TRISUBSTITUTED HYDROXYLAMINES FROM ALCOHOLS AND AMINES BY N-O BOND FORMATION
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Paragraph 0178-0179, (2021/11/26)
In one aspect, the disclosure relates to a method for the direct synthesis of complex N,N,O-trisubstituted hydroxylamines by N—O bond formation. In another aspect, the method can successfully be employed using a wide variety of commercially available alcohols and secondary amines and enables the construction of large fragment-based libraries of trisubstituted hydroxylamines for drug discovery purposes. Also disclosed are N,N,O-trisubstituted hydroxylamines having low basicity, high stability at ambient temperatures, and an inherent lack of reactivity towards acetylating and sulfonylating enzymes that confer mutagenicity on less-substituted hydroxylamines.
Diversity-oriented synthesis of N, N, O-trisubstituted hydroxylamines from alcohols and amines by N-O bond formation
Hill, Jarvis,Hettikankanamalage, Asiri A.,Crich, David
supporting information, p. 14820 - 14825 (2020/10/13)
Magnesium dialkylamides react with alcohol-derived 2-methyl-2-tetrahydropyranyl alkyl peroxides (MTHPs) in tetrahydrofuran at 0 °C to give N,N,O-trisubstituted hydroxylamines suitable for medicinal chemistry purposes in good to excellent yields. A wide range of secondary alkyl and aryl amines and primary and secondary alcohol-derived MTHPs are compatible with the described reaction which, coupled with the enormous diversity of commercially available alcohols and secondary amines, suggests broad applicability of the reaction in fragment-based library design.
Synthesis of Alkyl Silanes via Reaction of Unactivated Alkyl Chlorides and Triflates with Silyl Lithium Reagents
Mallick, Shubhadip,Würthwein, Ernst-Ulrich,Studer, Armido
supporting information, p. 6568 - 6572 (2020/09/02)
The reaction of unactivated secondary and primary alkyl chlorides as well as primary alkyl triflates with silyl lithium reagents to access tetraorganosilanes is reported. These nucleophilic substitutions proceed in the absence of any transition metal catalyst under mild conditions in moderate to very good yields. The silyl lithium reagents are readily generated from the corresponding commercially available chlorosilanes. Enantioenriched secondary alkyl chlorides react with high stereospecificity under inversion of configuration.
Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors
Bamborough, Paul,Chung, Chun-Wa,Furze, Rebecca C.,Grandi, Paola,Michon, Anne-Marie,Sheppard, Robert J.,Barnett, Heather,Diallo, Hawa,Dixon, David P.,Douault, Clement,Jones, Emma J.,Karamshi, Bhumika,Mitchell, Darren J.,Prinjha, Rab K.,Rau, Christina,Watson, Robert J.,Werner, Thilo,Demont, Emmanuel H.
, p. 6151 - 6178 (2015/08/24)
ATAD2 is a bromodomain-containing protein whose overexpression is linked to poor outcomes in a number of different cancer types. To date, no potent and selective inhibitors of the bromodomain have been reported. This article describes the structure-based optimization of a series of naphthyridones from micromolar leads with no selectivity over the BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold BET selectivity.
Synthesis of quaternary α-methyl α-amino acids by asymmetric alkylation of pseudoephenamine alaninamide pivaldimine
Hugelshofer, Cedric L.,Mellem, Kevin T.,Myers, Andrew G.
supporting information, p. 3134 - 3137 (2013/07/26)
The utility of pseudoephenamine as a chiral auxiliary for the alkylative construction of quaternary α-methyl α-amino acids is demonstrated. The method is notable for the high diastereoselectivities of the alkylation reactions, for its versatility with respect to electrophilic substrate partners, and for its mild hydrolysis conditions, which provide α-amino acids without salt contaminants. Alternatively, α-amino esters can be obtained by direct alcoholysis.
Deuterium Isotope Effects for Migrating and Nonmigrating Groups in the Solvolysis of Neopentyl-Type Esters
Shiner, V. J.,Tai, Jimmy J.
, p. 436 - 442 (2007/10/02)
α- and γ-deuterium rate effects on the solvolysis of (1-methylcyclohexyl)methyl, (1-methylcyclopentyl)methyl, and (1-methylcyclobutyl)methyl sulfonate esters have been measured and the solvolysis products examined by 2H NMR spectroscopy.The results indicate that the products of the solvolysis of all these sulfonate esters are predominantely ((*) 98percent) rearranged.In the solvolysis of (1-methylcyclohexyl)methyl triflate, rearranged products with methyl migration slightly dominate over those with ring expansion.Normal isotope effects, 1.057 in 80E and 1.073 in 97T, are observed for the methyl-d3 compound and an inverse effect, 0,963, is observed in 80E for the methylene-d4 compound.However, in the solvolysis of both (1-methylcyclopentyl)methyl and (1-methylcyclobutyl)methyl sulfonates, the major products are those of ring expansion.In these examples, inverse effects are observed for the methyl-d3-labeled species.The observed isotope effects can be separated into respective values of 0.927, 0.913 for the nonmigrating methyl-d3 group and 1.177, 1.224 for the migrating methyl-d3 group in the solvolysis of (1-methylcyclohexyl)methyl triflate and (1-methylcyclopentyl)methyl brosylate.This explains the relative intramolecular migratory aptitudes of CH3/CD3 of 1.20 - 1.30 and the low γ-d9 isotope effect in the solvolysis of neopentyl sulfonates previously reported and makes them consistent with a mechanism which involves neighboring carbon participation during ionization.
