380430-68-2

Usage

Uses

Reactant for:Rhodium-catalyzed cross-couplingPd-catalyzed Suzuki-Miyaura coupling

InChI:InChI=1/C11H16BNO4/c1-11(2,3)17-10(14)13-9-6-4-5-8(7-9)12(15)16/h4-7,15-16H,1-3H3,(H,13,14)

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 30418-59-8 3-Aminophenylboronic acid 
• 330793-09-4 tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenyl]carbamate 
• 13061-96-6 dihydroxy-methyl-borane 
• 13675-18-8 tetrahydroxydiboron 
• 143390-49-2 iodo-3-(tert-butyloxycarbonylamino)benzene 

Downstream Products

• 904086-01-7 3'-tert-Butoxycarbonylamino-biphenyl-3-carboxylic acid 
• 907566-73-8 methyl 2-{8-[3-(tert-butyloxycarbonylamino)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxylate 
• 1012863-31-8 N-(tert-butoxycarbonyl)-3-(diphenylmethyl)aniline 
• 1193709-00-0 2-[3-{(tert-butoxycarbonyl)amino}phenyl]-1,3,2-dioxaborolane 
• 1119772-74-5 t-Butyl [3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenyl]carbamate 
• 1233692-93-7 tert-butyl 4'-[2-methyl-1-(pyridin-4-yl)prop-1-enyl]biphenyl-3-ylcarbamate 
• 1269815-49-7 tert-butyl 3-(5-chloro-2-fluoropyridin-4-yl)-phenylcarbamate 
• 1269815-54-4 (R)-1-(tert-butyl-3-(4-(3-(tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)-5-chloropyridin-2-ylcarbamoyl)piperidine-1-carboxylate 
• 1269815-19-1 (R)-N-(5-chloro-4-(3-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)pyridin-2-yl)piperidine-3-carboxamide 
• 1269815-50-0 [3-(5-chloro-2-fluoro-pyridin-4-yl)-phenyl]-(tetrahydro-pyran-4-ylmethyl)-carbamic acid tert-butyl ester 
• 1269815-48-6 [3-(2-amino-5-chloro-pyridin-4-yl)-phenyl]-(tetrahydro-pyran-4-ylmethyl)-carbamic acid tert-butyl ester 
• 1309593-75-6 tert-butyl [3-(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl]carbamate 
• 1338718-97-0 C₁₅H₁₈N₄O₄ 
• 1355371-08-2 methyl 7-{3-[(tert-butoxycarbonyl)amino]phenoxy}-1,2,3,4-tetrahydronaphthalene-2-carboxylate 

Relevant academic research and scientific papers

Pd- And Ni-Based Systems for the Catalytic Borylation of Aryl (Pseudo)halides with B2(OH)4

Despite recent advancements in metal-catalyzed borylations of aryl (pseudo)halides, there is a continuing need to develop robust methods to access both early-stage and late-stage organoboron intermediates amendable for further functionalization. In particular, the development of general catalytic systems that operate under mild reaction conditions across a broad range of electrophilic partners remains elusive. Herein, we report the development and application of three catalytic systems (two Pd-based and one Ni-based) for the direct borylation of aryl (pseudo)halides using tetrahydroxydiboron (B2(OH)4). For the Pd-based catalyst systems, we have identified general reaction conditions that allow for the sequestration of halide ions through simple precipitation that results in catalyst loadings as low as 0.01 mol % (100 ppm) and reaction temperatures as low as room temperature. We also describe a complementary Ni-based catalyst system that employs simple unligated Ni(II) salts as an inexpensive alternative to the Pd-based systems for the borylation of aryl (pseudo)halides. Extrapolation of all three systems to a one-pot tandem borylation/Suzuki-Miyaura cross-coupling is also demonstrated on advanced intermediates and drug substances.

MITOGEN-ACTIVATED PROTEIN KINASE KINASE 7 INHIBITORS

Provided are compounds that act as covalent inhibitors of mitogen-activated protein kinase kinase 7 (MKK7 enzyme), method of preparation and uses thereof.

Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids

Boronic acids are an increasingly important compound class for many applications, including C-C bond formation reactions, medicinal chemistry, and diagnostics. The deprotection of boronic ester intermediates is frequently a problematic and inefficient step in boronic acid syntheses. We describe an approach that highly facilitates this transformation by leveraging the volatility of methylboronic acid and its diol esters. The method is performed under mild conditions, provides high yields, and eliminates cumbersome and problematic purification steps.

Trisubstituted Imidazoles with a Rigidized Hinge Binding Motif Act As Single Digit nM Inhibitors of Clinically Relevant EGFR L858R/T790M and L858R/T790M/C797S Mutants: An Example of Target Hopping

The high genomic instability of non-small cell lung cancer tumors leads to the rapid development of resistance against promising EGFR tyrosine kinase inhibitors (TKIs). A recently detected triple mutation compromises the activity of the gold standard third-generation EGFR inhibitors. We have prepared a set of trisubstituted imidazoles with a rigidized 7-azaindole hinge binding motif as a new structural class of EGFR inhibitors by a target hopping approach from p38α MAPK inhibitor templates. On the basis of an iterative approach of docking, compound preparation, biological testing, and SAR interpretation, robust and flexible synthetic routes were established. As a result, we report two reversible inhibitors 11d and 11e of the clinically challenging triple mutant L858R/T790M/C797S with IC50 values in the low nanomolar range. Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC50 value of 1 nM against the EGFR L858R/T790M double mutant. Target binding kinetics and metabolic stability data are included. These potent mutant EGFR inhibitors may serve as a basis for the development of structurally novel EGFR probes, tools, or candidates.

Small molecule thienopyrimidine-based protein tyrosine kinase inhibitors

Various thienopyrimidine-based analog compounds are able to selectively inhibit the Src family of tyrosine kinases. These compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, or viral infections.

A novel redox-sensitive protecting group for boronic acids, MPMP-diol

A new boronic acid protecting group, 1-(4-methoxyphenyl)-2-methylpropane-1, 2-diol (MPMP-diol), has been developed. Both protection and deprotection can be accomplished under mild conditions with quantitative conversions. The deprotection can be carried out using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).

Rational design of diflunisal analogues with reduced affinity for human serum albumin

Many lead compounds bind to serum albumin and exhibit markedly reduced efficacy in vivo as compared to their potency in vitro. To aid in the design of compounds with reduced albumin binding, we performed nuclear magnetic resonance (NMR) structural and binding studies on the complex between domain III of human serum albumin (HSA-III) and diflunisal, a cyclooxygenase inhibitor with antiinflammatory activity. The structural studies indicate that the aromatic rings of diflunisal are involved in extensive and specific interactions with hydrophobic residues that comprise the binding pocket in subdomain IIIA. The carboxylic acid of diflunisal forms electrostatic interactions with the protein similar to those observed in the X-ray structure of HSA complexed to myristic acid. In addition to the structural studies, NMR-derived binding constants were obtained for diflunisal and closely related analogues to develop a structure-affinity relationship for binding to subdomain IIIA. On the basis of the structural and binding data, compounds were synthesized that exhibit more than a 100-fold reduction in binding to domain III of HSA, and nearly a 10-fold reduction in affinity for full length albumin. Significantly, several of these compounds maintain activity against cyclooxygenase-2. These results suggest a rational strategy for designing out albumin binding in potential drug molecules by using structure-based design in conjunction with NMR-based screening.