3-Substituted imidazo pyridines

Imidazo[l,2-n]pyridine, 5-methyl-2-methylthio-3-substituted synthesis, 5, 632... 

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

Cyclization of substituted vinylic imidazo[l,2-tf]pyridines has been used to synthesize angular tricyclic systems. For example, reaction of 136 with ethyl azidoacetate 137 to give 138 followed by cyclization furnishes 139 (Scheme 10) <2001JOC6576>. 

Table 12 Aromatic electrophilic substitution at C-3 in imidazo[1,2-a]pyridines...

No definitive studies on IR spectroscopy in this group have been found since the publication of Chapter 7.08 in <1996CHEC-II(7)283>. IR structural observations have only been used as supporting evidence for structure elucidation. For example, the IR spectra of 2-substituted-3-oxoisothiazolo[5,4- ]pyridines 43-58 have been reported (Table 9) <1998FES504>. The IR data for imidazo[4,5- ] and imidazo[4,5-. 

Antiviral 2,5-disubstituted imidazo[4,5-f]pyridines have been reported for the treatment of hepatitis C <2007BML390, 2007BML5111>. A method for the preparation of substituted l//-imidazo[4,5-f]pyridines as immune response modifiers has been reported <2007W0092641>. 6-Phenyl-l//-imidazo[4,5-f]pyridine-4-carbo-nitrile derivatives have been reported to act as cathepsin K and S inhibitors <2007USP179138>. Imidazo[4,5-4pyridine derivatives have also been prepared as C3A receptor antagonists <2007W0034277>. 

The I/Mg-exchange reaction can be extended to the use of iodo-substituted pyridines uracils , purines" , imidazoles , quinolines, imidazo[l,2-a]-pyridines, pyrroles ... 

Interaction of substituted dienediamines with ethylenediamine yields im-idazo[3,2-n]pyridine derivatives (95JHC477). 3-Arylaminoindoles, with distinct enamine properties, are the starting materials for the synthesis of indolo[3,2-b]quinoline derivatives [96KFZ(7)42]. a-Carboline derivatives can be obtained from enamine-based 3-dimethylamino-2-indolinones [96KFZ(9)35, 96KFZ(10)32], The synthesis and transformation of enamines based on the pyrido[l,2-n]pyrazine ring system into imidazo[l,2-n]pyridine and imidazo[l,2-a]pyrimidine derivatives have been reported... 

Reactions with methylphenylcyclopropenone (154) provided an opportunity to compare the reactivities of the two different C—CO bonds. The reaction of 2-aminopyridines with methylphenylcyclopropenone (154) proceeded more slowly than with the diphenyl analog (153). In ether, formation of the ds-2-oxopyrido[l,2-a]pyrimidines (158 R1 = Me) and/or the imidazo[l,2-c<]pyridines (162) was observed, indicating that the cycloaddition proceeds via cleavage of the PhC—CO bond. The methyl-substituted trans-2-oxopyrido[l,2-a]pyrimidine (160 R1 = Me) was only detected in the reaction mixture of 2-amino-3-methylpyridine, where the H NMR spectrum exhibited signals assigned to 160 (R1 = Me, R = 9-Me). The compound was not isolated. The imidazo[l,2-a]pyridines (162) readily hydrolyzed to the acids (163), work-up therefore leading mainly to isolation of the acids. 

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