Azaindole derivatives

Cossy and coworkers described a precise combination of a Heck and a Suzuki-Miyama reaction using ynamides and boronic acids to give indole and 7-azaindole derivatives [46]. Thus, reaction of 6/1-73 with 6/1-74 using Pd(OAc)2 as catalyst led to 6/1-75 in 68% yield (Scheme 6/1.18). 

The three-component coupling systems explored extensively by Zhu has been used to synthesize tricyclic azaindole derivatives 153 from 150, heptanal 151, and an aryl- or alkylamine 152 (Equation 35) <20050L239>. 

SCHEME 3.67 Chemical structures of deep blue 7-azaindole derivatives. 

Q. Wu, J.A. Lavigne, Y. Tao, M. DTorio, and S. Wang, Novel blue luminescent/electrolumines-luminescent 7-azaindole derivatives l,3-di(7V-7-azaindolyl)benzene, l-bromo-3,5-di(Y-7-azaindo-lyl)benzene, 1,3,5-tri(/V-7-azaindolyl)benzene, and 4,4 -di(7V-7-azaindolyl)biphenyl, Chem. Mater., 13 71-77 (2001). 

The benzenesulfonyl substituent has also been used in conjunction with the lithiation of an azaindole derivative (86FRP2574406 89FRP26274931), and thus 1-benzenesulfonyl-1//-pyrrolo[3,2-c ]pyridine was able to be successfully lithiated and alkylated with p-methoxybenzaldehyde, although reaction with more hindered ketones could not be achieved (Scheme 19)[91JCS(P1)3I73]. 

Certain 2-amino-3-ketones 193 also serve, via the agency of hydrochloric acid, as intermediates for the synthesis of 7-azaindole derivatives 194 (Scheme 57) (88JOC2740). 

Recent work on the thermal indolization of arylhydrazones has introduced new synthetic possibilities for azaindoles. Kelly et al. refluxed cyclohexanone and deoxybenzoin 2-pyridylhydrazones in diethylene glycol to give 5,6,7,8-tetrahydro-a-carboline (42, R = H) and 2,3-diphenyl-7-azaindole in 70 and 56% yields, respectively, compared with 53 and 12% reported earlier. Similarly, y-carboline 29 was obtained in 95 % yield from cyclohexanone 4-pyTidylhydrazone (lit. 48% ). Several 7-azaindole derivatives were prepared in the same manner. The yields ranged from 5 % for azaindolenine (31) to 88% for 3-phenyl-7-azaindole. 3,3-Dimethyl-7-azaindolenine was obtained in 47 % yield from the isobutyralaldehyde hydrazone. The novel cyclic compounds 40 and 41 were obtained from the 2-pyridylhydrazones of cyclopentanone, a-indanone, and a-tetralone in 67, 95, and 77% yields, respectively. Unfortunately, all attempts to cyclize the acetone, pyruvic acid, and ethyl pyruvate hydrazones were unsuccessful. Also, cyclohexanone and methyl ethyl ketone 5-nitro-2-... 

The limitations of this approach to the synthesis of azaindoles are (i) unavailability of other amino- or chloroethylpyridines suitable for cyclization (ii) adaptation to the synthesis of the other azaindoles and Hi) the necessity of high temperature and pressure for cyclization, requiring specialized equipment for large-scale preparations. For those applications already investigated it does offer a unique and useful method for the synthesis of a variety of 7-azaindole derivatives. 

To date, none of the above syntheses appears to be a suitable route to nonoxygenated azaindole derivatives. 

Infrared spectral data available for those azaindole derivatives which are not completely aromatic, i.e., azaindolenines, azaindoxyls, and azaoxindoles, are listed in Table V. 

A patent describing the synthesis of azalogs of the drug indo-methicin claims the 7-azaindole derivative to have anti-inflammatory, analgesic, and antipyretic properties. 

Pharmacological data for several of the other azaindole derivatives of biological interest have not appeared as yet. Those of particular interest are 12-azadeserpidine, 5-azatryptamine, the several 4-methyl-7-azatryptamines, and the azaharman analogs. ... 

Lober, S., Hubner, H., Gmeiner, P. Fused azaindole derivatives molecular design, synthesis and in vitro pharmacology leading to the preferential dopamine D3 receptor agonist FAUC 725. Bioorg. Med. Chem. Lett. 2002, 72(17), 2377-2380. 

Papalia GA, Giannetti AM, Arora N, Myszka DG (2008) Thermodynamic characterization of pyrazole and azaindole derivatives binding to p38 mitogen-activated protein kinase using Biacore T100 technology and van t Hoff analysis. Anal Biochem 383 255-264... 

Regueiro-Ren A (2012) Inhibitors of Human Immunodeficiency Virus Type (HIV-1) attachment IX. Structure-activity relationships associated with 4-Fluoro-6-azaindole derivatives leading to the identification of l-(4-Benzoyl-piperazin-l-yl)-2-(4-fluoro-7-[l,2,3]triazol-l-yl-lH-pyrrolo[2,3-c]pyridin-3-yl)-ethane-l,2-dione (BMS-585248) (Manuscript in preparation)... 

Knochel invented a protocol for the efficient coupling of heteroaryl-methylzinc chlorides with various other functional groups. A 7-azaindole derivative 304, was allylated with 305 using copper catalysis (140L2422). 

New substituted indole and azaindole derivatives as anti-HIV agents 13MRM1700. 

Formation of 5-azaindoles Derivatives 2-1 from One Molecule of the Bis (alkynyi)silane with Three Moiecuies of Identical Organonitriles To a toluene... 

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