Improved synthesis of pyrrolo[1,2-c]pyrimidine and derivatives

An improved synthesis of pyrrolo[1,2-c]pyrimidine derivatives by cyclocondensation of pyrrole-2-carboxaldehydes with tosylmethyl isocyanide followed by desulfonylation of the resulting 2-tosylpyrrolo[1,2-c]pyrimidines with sodium amalgam is described.We thank the Comissió Interdepartamental de Reserca i Innovació Tecnológica (CIRIT) for financial support (project QFN91-4619 ) and the Ministerio de Educación y Ciencia for a grant (J.M.M.

Synthesis and pharmacology of alkanediguanidinium compounds that block the neuronal nicotinic acetylcholine receptor

Taking as models the polyamine toxin fraction FTX from the funnel-web spider venom, and the guanidinium moiety of guanethidine, a series of azaalkane-1,omega-diguanidinium salts were obtained. Some of them blocked ion fluxes through the neuronal nicotinic receptors for acetylcholine (nAChR). The blockade was exerted at submicromolar concentrations, suggesting a highly selective interaction with the nAChR. In fact, the active compounds on the nAChR ion channel did not recognize the voltage-dependent Na+ or Ca2+ channels of bovine adrenal chromaffin cells. Therefore, these compounds may be useful tools to clarify the functions of nAChR receptors in the central and peripheral nervous systems.Fundación Ramón Arece

Pyridinium-N-(2-Pyridyl)aminides: a selective approach to substituted 2-aminopyridines

Differently substituted 2-aminopyridines have been prepared in two steps from pyridinium-N-(2-pyridyl)aminide, by reaction with the corresponding electrophiles and reduction of the N-N bond.Ministerio de Educación y Cienci

Chemoselective addition of grignard reagents to alkoxycarbonylalkyl-N-imidazolium-N-methyl amides: synthesis of 4-oxo and homologous esters

A method for the synthesis of 4-oxo and homologous esters is achieved by metalation of alkoxycarbonylalkyl-N-imidazolium-N-methyl amides with 1equiv of LDA followed by highly chemoselective addition of 1 equiv of a Grignard reagent.Ministerio de Educación y Cienci

Halogenation of pyridinium-N-(2'-pyridyl)aminide: an easy synthesis of halo-2-aminopyridines

The regioselective halogenatmn of pyrldmium-N-(2’-pyridyljaminide 1 with N-chloro,\ud bromo or iodosuccinimtde under mild conditions IS described. The method, combined with a\ud reductmn of the N-N bond, allows an easy preparation of 5-h& and 3,5-dihalo-Z-aminopyridines 4The authors wish to thank the Comisión Interministerial de Ciencia y Tecnología (C.I.C.Y.T.) for financial support (Project PB90-0284) and to Lilly S. A. for one studentship (C.B.

Synthesis of aldehydes from acyl chlorides via 1-(acylmethylamino)-3-methylimidazolium salts

The reaction of acyl chlorides with 1-amino-3-methylimidazolium salts, followed by N-methylation of the resulting H-aminides, afforded 1-(acylmethylamino)-3-methylimidazolium salts which, upon treatment with DIBALHgave aldehydes in good yields. A nalogously, dialdehydes were obtained from the corresponding bis-salts.The authors are grateful for grant (MAH) from Ministerio de Educación y Ciencia\ud and financial support from Comisión Interministerial de Ciencia y Tecnología (CICYT) through the project\ud PB90-028

Synthesis of carbonyl and dicarbonyl compounds from organometallic reagents and N-imidazolium-N-methyl amides and bis-amides

A new method for the synthesis of selective acylating agents is described from the reaction of carboxylic acids with 3-methyl-1-methylamino-3H-imidazol-1-ium salts in the presence of appropriate coupling reagents. The amides and bis-amides thus prepared reacted selectively with organometallics to afford ketones and diketones and with DIBALH to give aldehydes and dialdehydes in high yields.The authors acknowledge the Comisió Interdepartamental de Recerςa i Innovació Tecnológica (CIRIT, project QFN94-4619) for financial support and the Ministerio de Educaci6n y Ciencia for a studentship (M.A.H.)

A stereoselective synthesis of (R)-(-)-rolipram from L-glutamic acid

A stereoselective synthesis of (R)-(-)-rolipram from L-glutamic acid is described. The key step is a stereoselective Michael addition of an arylcuprate to a modified pyroglutamic derivative which acts as the template to induce the stereoselectivity. Facile manipulation of the enantiomerically pure Michael product afforded the expected therapeutic agent.We gratefully acknowledge ZAMBON GROUP for studentships (to A. D. and J. S.) and financial support

Unexpected N-C bond fission of fused N-alkylbenzimidazolium salts. A new approach to pyrido[1,2-a]- or pyridazino[1,6-a]benzimidazoles

The reaction of N-carboxymethylpyrido[1,2-a]- and pyridazino[1,6-a]benzimidazolium salts with thionyl chloride resulted in an N-C bond fission, yielding the corresponding pyrido[1,2-a]- and pyridazino[1,6-a]benzimidazoles. A similar dealkylation process was observed when analogous N-propargylic derivatives were treated with Cu (II) acetate.Universidad de Alcal

Optimized synthesis of di, tri and tetrafused pyridazinium cations

By combining two complementary statistical techniques (fractional factorial experimental design and simplex operation) the synthesis of the parent pyrido[1,2-b]-pyridazinium cation has been successfully carried out (the yield was improved from less than 10 to 65%) by basic condensation of 2-methyl-1-aminopyridinium mesitylenesulfonate and [1,4]dioxane-2,3-diol. Using the optimized reaction conditions, other related heterocyclic cations could be prepared, and two interesting examples are now reported.Ministerio de Educación y CienciaUniversidad de Alcal