Solid-phase approach towards the synthesis of functionalized imidazo[1,2-b]pyrazol-2-ones

Published in: Journal, Volume : 45, Issue : 6, Pages : 1275-1277

DOI : 10.1016/j.tetlet.2003.11.135

Author : Blass, Benjamin E.; Srivastava, Anil; Coburn, Keith R.; Faulkner, Amy L.; Janusz, John J.; Ridgeway, James M.; Seibel, William L.

Abstract : The solid-phase synthesis of a series of imidazo[1,2-b]pyrazol-2-ones, an interesting 5,5-fused ring system, based on diverse set of hydrazine acids and malonitriles is described. The method involves formation of 5-aminopyrazoles on solid support and subsequent cyclizative cleavage off the resin. Compounds were obtained in acceptable to excellent yields and are suitable for biol. evaluation without further purification Example compounds thus prepared included 1,8-dihydro-3-[[4-(trifluoromethoxy)phenyl]methyl]-6H-imidazo[1,2-b]thieno[3,4-d]pyrazol-2(3H)-one (I) and 6-(1,1-dimethylethyl)-3-[[4-(trifluoromethoxy)phenyl]methyl]-1H-imidazo[1,2-b]pyrazol-2(3H)-one (II).

Novel Petasis boronic acid reactions with 1,3,5-tri-oxygenated benzenes

Published in: Journal, Volume :44, Issue : 49, Pages : 8861-8863

DOI : 10.1016/j.tetlet.2003.09.178

Author : Naskar, Dinabandhu; Roy, Amrita; Seibel, William L.

Abstract : 1,3,5-Tri-Oxygenated benzenes can serve as substrates for the Petasis boronic acid reaction, providing a practical synthetic route for the two C-C bond formation of α-(1,3,5-tri-oxygenated phenyl)carboxylic acids. The scope and limitations of this method were examined

Hydroxylamines and sulfinamide as amine components in the Petasis boronic acid-Mannich reaction: synthesis of N-hydroxy or alkoxy-α-aminocarboxylic acids and N-(tert-butyl sulfinyl)-α-amino carboxylic acids

Published in: Journal, Volume :44, Issue : 49, Pages : 8865-8868

DOI : 10.1016/j.tetlet.2003.09.179

Author : Naskar, Dinabandhu; Roy, Amrita; Seibel, William L.; Portlock, David E.

Abstract : An efficient synthesis of N-hydroxy or alkoxy-α-aminocarboxylic acids and N-(tert-Bu sulfinyl)-α-amino carboxylic acids was developed from N,O-alkyl or hydroxylamines and tert-Bu sulfinamide utilizing a Petasis boronic acid-Mannich reaction. The scope and limitations of this method were examined

The synthesis of aza-β-lactams via tandem Petasis-Ugi multi-component condensation and 1,3-diisopropylcarbodiimide (DIC) condensation reaction

Published in: Journal, Volume :44, Issue : 33, Pages : 6297-6300

DOI : 10.1016/s0040-4039(03)01524-7

Author : Naskar, Dinabandhu; Roy, Amrita; Seibel, William L.; West, Laura; Portlock, David E.

Abstract : The synthetic utility of a tandem Petasis-Ugi multi-component condensation and 1,3-diisopropylcarbodiimide condensation reactions have been employed to efficiently prepare two to four-dimensional libraries of aza-β-lactams.

Positional isomerization of quinine and quinidine via rhodium on alumina catalysis: practical one-step synthesis of Δ3,10-isoquinine and Δ3,10-isoquinidine

Published in: Journal, Volume : 44, Issue : 28, Pages : 5365-5368

DOI : 10.1016/s0040-4039(03)01180-8

Author : Portlock, David E.; Naskar, Dinabandhu; West, Laura; Seibel, William L.; Gu, Titan; Krauss, Howard J.; Peng, X. Sean; Dybas, Paul M.; Soyke, Edward G.; Ashton, Stephen B.; Burton, Jonathan

Abstract : The synthesis of Δ3,10-isoquinine (5Z,5E) and Δ3,10-isoquinidine (6Z,6E) was achieved in one-step through positional isomerization of the terminal alkene in the parent cinchona alkaloids using catalytic amounts of 5% Rh/Al2O3 and excess hydrochloric acid in refluxing 50% aqueous EtOH. The products were obtained in good yields as a mixture of E and Z geometric isomers and fully characterized using spectroscopic methods.

Solid-phase synthesis of five-dimensional libraries via a tandem Petasis-Ugi multi-component condensation reaction

Published in: Journal, Volume : 44, Issue : 27, Pages : 5121-5124

DOI : 10.1016/s0040-4039(03)01119-5

Author : Portlock, David E.; Naskar, Dinabandhu; West, Laura; Ostaszewski, Ryszard; Chen, Jack J.

Abstract : Five-dimensional libraries of dipeptide amides are readily prepared using a solid-phase tandem Petasis-Ugi multi-component condensation protocol on either a RINK amine or Universal RINK isonitrile resin. The method is practical and can be automated to prepare a large number of compounds useful for high throughput biol. screening.

A tandem Petasis-Ugi multi component condensation reaction: solution phase synthesis of six dimensional libraries

Published in: Journal, Volume : 44, Issue : 3, Pages : 603-605

DOI : 10.1016/s0040-4039(02)02619-9

Author : Portlock, David E.; Ostaszewski, Ryszard; Naskar, Dinabandhu; West, Laura

Abstract : Amino acids with three points of diversity generated from the Petasis boronic acid-Mannich reaction can be used as one of the four components of the Ugi condensation to prepare six dimensional libraries of dipeptide amides. Thus, petasis amino acid substrate Me2NCH2CO2H underwent Ugi reaction with p-MeC6H4CH2NH2, PhCH2CH2CHO, and 2,6-Me2C6H3NC to afford 42% Me2NCH2CON(CH2C6H4Me-p)CH(CH2CH2Ph)CONHC6H3Me2-2,6.

A simple method for the preparation and selective functionalization of 4,5-diaminopyrazoles

Published in: Journal, Volume : 44, Issue : 14, Pages : 3009-3011

DOI : 10.1016/s0040-4039(03)00398-8

Author : Blass, Benjamin E.; Srivastava, Anil; Coburn, Keith R.; Faulkner, Amy L.; Seibel, William L.

Abstract : A simple procedure for the synthesis and further functionalization of 4,5-diaminopyrazoles using mild conditions is reported herein. The desired products were obtained in good yield, and the structures were confirmed by X-ray crystallog.

Applications of solid supported azide anion. A one-pot, two-step preparation of functionalized 1,2,3-triazoles

Published in: Journal, Volume : 44, Issue : 10, Pages : 2153-2155

DOI : 10.1016/s0040-4039(03)00180-1

Author : Blass, Benjamin E.; Coburn, Keith R.; Faulkner, Amy L.; Seibel, William L.; Srivastava, Anil

Abstract : Functionalized 1,2,3-triazoles were prepared in a one-pot, two-step synthesis from alkyl halides and alkynes using a polymer supported azide. Two different base resins were examined The chem. is suitable for the preparation of combinatorial libraries.

Solid-phase synthesis of functionalized 1,2,4-triazin-6-ones

Published in: Journal, Volume : 43, Issue : 45, Pages : 8165-8167

DOI : 10.1016/s0040-4039(02)01956-1

Author : Blass, Benjamin E.; Coburn, Keith R.; Faulkner, Amy L.; Liu, Song; Ogden, Adam; Portlock, David E.; Srivastava, Anil

Abstract : The solid supported synthesis of functionalized 1,2,4-triazin-6-ones from resin bound amino acids and acid chlorides is described. A thioamide intermediate is generated with Lawesson’s reagent, and the final products are cyclized and cleaved from resin with hydrazine. The products are obtained in good yield and purity.