Synthesis and Pharmacoclogical Activity of a Pyrido[3',4':5,4]pyrrolo[1,2-c][1,4]benzodiazepine-3,10-dione, a New Benzodiazepine-b-carboline Type Hybrid Molecule

Synthesis of 3-Deaza-β-hydroxyhistidine Derivatives and Their Use for the Preparation of Substituted Pyrrolo[2,3-c]pyridine-5-carboxylates via the Pictet−Spengler Reaction

“…The presence, in the 1 H NMR spectrum of 9 , of two doublets at 6.82 and 7.80 ppm ( J = 3.6 Hz) corresponding to the two vinylic protons of the pyrrole ring indicates that cyclization had indeed occurred at the C-2 position of 8 rather than at the C-4 position. Moreover, dehydrogenation of the tetrahydro derivative 9 under the same conditions known to dehydrogenate tetrahydro-β-carboline derivatives (reflux in xylene in the presence of palladium on carbon) , gave 6-azaindole 10a, the NMR data ( 1 H, 13 C) for which were practically identical to those of analogous 6-azaindoles we have prepared using other methodologies (see also below). − …”

“…In relation to several pharmacologically oriented research programs in our own laboratory, we have been interested in developing efficient syntheses of multiply substituted pyrrolo[2,3- c ]pyridines (hereinafter referred to as 6-azaindoles), particularly those carrying a carboxylate group at the C-5 position (e.g., 1 , Scheme ). While this class of compounds has generally been prepared by construction of the fused pyrrole ring from a suitably substituted pyridine ring, − we have recently described the use of a complementary strategy in which the pyridine ring is built up from a pyrrole precursor, that is, from a pyrrole-2-carboxaldehyde ) suggests that 6-azaindoles of type 1 should also be available via dehydrogenation of the corresponding tetrahydro derivatives 2 , themselves prepared by a Pictet−Spengler-type condensation of an aldehyde, R‘CHO, with the 3-deazahistidine derivative 3 .…”

Development of an Efficient and Scalable Process of a Respiratory Syncytial Virus Inhibitor

“…An inexpensive alternative route to 3 was developed (Scheme ). 4-Hydroxypyridine 10 was nitrated using potassium nitrate in sulfuric acid . This reaction is highly exothermic, and the addition rate of solid KNO 3 to the reaction mixture was carefully controlled to avoid an uncontrolled exotherm and vigorous off-gassing of nitrogen oxides.…”

Síntese e reatividade de azaindóis: aplicações na preparação de moléculas de interesse biológico

“…Os ésteres do ácido β-carbolina-3-carboxílico 35 (Figura 4) são [35][36][37][38][39][40][41] sintetizaram vários derivados do ácido 6-azaindol-5-carboxílico, usando várias rotas de síntese.…”

“…Após condensação com dimetilformamida dimetilacetal e ciclização da amina vinílica resultante, o azaindol 45 é obtido. A oxidação do aldeído leva ao ácido 46 e, após tratamento com metanol em meio ácido, ao éster metílico 47 (Esquema 14) Os substituintes podem ser introduzidos na posição C-3, após formação do azaindol, via o derivado azagramina 58 36 (Esquema 17), ou via o derivado 3-formil-6-azaindol 61 (Esquema 18), preparado por reação de 57 com 1,1-diclorometil metil éter em presença de cloreto de alumínio 39 . Usando como amina o 2-amino-3,3-dietoxibutirato na etapa de condensação com o pirrol 66 40 , é possível introduzir um grupo metila em posição 5, que pode posteriormente ser funcionalizado (Esquema 19).…”