Nobuyoshi Yasuda

A new general method for preparation of N-methoxy-N-methylamides. Application in direct conversion of an ester to a ketone

Abstract The reaction of an ester with N , O -dimethylhydroxylamine and a suitable organomagnesium reagent or lithium amide base provides a general method for the preparation of N -methoxy- N -methylamides. Application in the direct conversion of a highly hindered ester to a ketone, the azasteroid 5α-reductase inhibitor MK-0434, is described.

Application of cross-coupling reactions in Merck

Abstract Process design and development of drug candidates using cross-coupling reactions as key steps are discussed. In the anti-MRS carbapenem project, all drug candidates were prepared effectively in a few steps from the commercially available diazo intermediate by either Suzuki–Miyaura cross-coupling or Stille–Migita cross-coupling, demonstrating the versatility, effectiveness, functional group tolerability, and mild reaction conditions of cross-coupling methods.

N-cyclopropylation of indoles and cyclic amides with copper(II) reagent.

Copper-mediated coupling reactions of cyclopropylboronic acid with indoles and cyclic amides are described. The process utilizes catalytic or stoichiometric amounts of copper(II) acetate, DMAP, and NaHMDS at 95 degrees C under an atmosphere containing oxygen. A variety of functional groups remain intact throughout the reaction.

Expedient Synthesis of 3-Alkoxymethyl- and 3-Aminomethyl-Pyrazolo[3,4-b]pyridines

An effective strategy has been developed for the preparation of 3-alkoxymethyl-pyrazolo[3,4-b]pyridines, compounds that are currently not readily accessible by existing synthetic methods. Further manipulation of these compounds allows for access to 3-alkoxymethyl-pyrazolo[3,4-b]pyridines with a variety of substitution patterns as well as 3-aminomethyl-pyrazolo[3,4-b]pyridines.

Preparation of 2-aryl- and 2-alkenyl-substituted carbapenems under mild suzuki cross-coupling conditions

Abstract An extraordinarily mild procedure for the synthesis of 2-aryl- and 2-alkenyl-substituted carbapenems via palladium-catalyzed coupling of a vinyl triflate with aryl or vinyl boronic acids is described. A major advantage of this procedure is the use of nontoxic boronic acid intermediates in place of highly toxic organostannane compounds which are used in the corresponding Stille cross-coupling reactions.

Practical Synthesis of Chiral N,N′-Bis(2′-pyridinecarboxamide)-1,2-cyclohexane Ligands

A simple and scalable procedure for the preparation of chiral ligands 1and 2from trans-1,2-diaminocyclohexane and 2-picolinic acid is described.

Stereoselective [2,3]-wittig rearrangement of (1S,2R)-1-amino-indan-2-ol derived amide enolates

Abstract An efficient, diastereoselective [2,3]-Wittig rearrangement of α-allyloxy-amide enolates has been developed using (1S,2R)-1-amino-indan-2-ol as a chiral auxiliary. After auxiliary removal, the resultant optically active α-hydroxy acids have been transformed to functionalized amino acid derivatives.

Practical and cost-effective manufacturing route for the synthesis of a β-lactamase inhibitor.

Compound 1, a potent and irreversible inhibitor of β-lactamases, is in clinical trials with β-lactam antibiotics for the treatment of serious and antibiotic-resistant bacterial infections. A short, scalable, and cost-effective route for the production of this densely functionalized polycyclic molecule is described.

Development of a practical, asymmetric synthesis of the hepatitis C virus protease inhibitor MK-5172.

The development of a practical, asymmetric synthesis of the hepatitis C virus (HCV) protease inhibitor MK-5172 (1), an 18-membered macrocycle, is described.

A highly efficient synthesis of 2-[3-aminopropyl]-5,6,7,8-tetrahydronaphthyridine via a double Suzuki reaction and a Chichibabin cyclization

Abstract Synthesis of 2-[3-aminopropyl]-5,6,7,8-tetrahydronaphthyridine was accomplished via a one-pot double Suzuki reaction followed by deprotection and a highly regioselective intramolecular Chichibabin cyclization. A variety of reactions conditions were screened for the Chichibabin cyclization including choice of base, solvent and reaction temperature.