Imidazo pyridine derivatives

Methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2-propynyl)-imidazo-[l,2-a]-pyridine has been investigated as an imidazo-pyridine derivative and an orally effective antiulcer agent potentially useful as an inhibitor of ATPase. The title compound has been obtained in... 

This reaction procedure has also been used for the synthesis of oxazolo[3,2-fl]pyridine and imidazo[l,2-fl]pyridine derivatives, and the numerous variations studied, allowing changes of the substituent pattern and the number and position of the nitrogen atoms in the six-membered ring, are described in Chapters 4.10 and 4.29. 

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... 

Reaction of the pyridine derivative (303 R = CH(Ph)2) with ethyl orthoformate afforded only the imidazo[4,5-c]pyridine (304) in good yield <73JMC292>. A later study <87JMC1746> has reported the isolation of mixtures of both imidazo[4,5-c]pyridines (304) and imidazo[4,5-6]pyridines (305) (Equation (23)) with the isomeric ratio being dependent on the steric bulk of the 4-amino substituent. When compound (303 R = phenyl) was cyclized with ethyl orthoformate a mixture of both isomers (304) and (305) was isolated in a 1 2 ratio. However, if compound (303 R = benzyl) is used a 1 10 ratio of the products (304) and (305) is obtained. When a phenethylamino group is positioned at C-4 only the isomer (304) is formed in the reaction. Interestingly, the reaction of the derivatives (306) or (308) with benzaldehyde at room temperature for 64 h furnished only modest yields of the products (307) and (309), respectively (Equation (24)). No imidazo[4,5-c]pyridine isomer was detected in these reactions. 

Burstein C, Lehmann CW, Glorius F (2005) Imidazo[l,5-a]pyridine-3-ylidenes-pyridine derived N-heterocyclic carbene ligands. Tetrahedron 61 6207-6217... 

In earlier investigations by the author (5), mGluR5a receptor antagonists consisting of imidazo[l,2-a]pyridine derivatives, (II), were prepared and were effective in treating Alzheimer s disease. 

Quinolones, (I), and lH-imidazo[4,5-b]pyridine derivatives, (n), effective as methionyl t-RNA synthetase inhibitors were previously prepared by the author (2,3), respectively. 

Warshakoon NC, Wu S, Boyer A, Kawamoto R, Sheville J, Renock S, Xu K, Pokross M, Evdokimov AG, Walter R, Mekel M. A novel series of imidazo[l,2-a]pyridine derivatives as HIF-lalpha prolyl hydroxylase inhibitors. Bioorg. Med. Chem. Lett. 2006 16 5598-5601. 

Musicki, B., and Vevert, J.-P., Synthesis of conformationally restricted analogues of an angiotensin II receptor antagonist. General synthetic approach to functionalized imidazo[l,5-a]pyridine derivatives, Tetrahedron Lett., 35, 9391, 1994. 

Treatment of 2-alkyl- or 2-hydroxymethyl-l-aminopyridinium salts with acyl or aroyl chlorides in the presence of base causes cyclization to pyrazolo[l,5-a]pyridine derivatives. If the 3-position is unsubstituted, acylation occurs at this position under the reaction conditions (Eq. 13).18141 There is good evidence that the initial step is acylation of the iV-amino group. This reaction has been extended to the synthesis of various bridgehead nitrogen heterocyclic systems including pyrazolodiazines (11),9 pyrazolo[5,l- ]thiazole (12),142 and imidazo[l,2-h]pyrazole (13).142... 

Salts 470 72 were obtained from amine 427 and bromoketones or bromoacet-aldehyde. They were later converted into imidazo[4,5-c]imidazo[l,2-a]pyridine derivatives 473, 474 and 477 by treatment with alkali. However, ketones like phenacyl bromide and its />-nitro- and /7-methyl-substituted analogues do not give stable quaternary salts with amine 427 yielding instead tricyclic bases 475 and 476 (86KG227). 

Mishra and Ghosh (2011) found that Cu(l)-NaHS04 Si02 could be utilized as a novel and efQdent heterogeneous catalyst for the synthesis of imidazo[l,2-fl]pyri-dines using three-component reactions of 2-aminopyridines, aldehydes, and terminal alkynes in one pot (Scheme 4.56). Under this catalytic systan, diverse imidazo[l,2-fl]pyridine derivatives were generated in moderate to excellent yields. 

The synthesis of imidazo[l,2- ]pyridine derivatives from simple substituted pyridines is also developed recently. Fu et al. reported an efficient Cul-catalyzed aerobic oxidative C-H functionalization of substituted pyridines with N-(alkylidene)-4//-l,2,4-triazol-4-ammes leading to imidazo[l,2- ] pyridine derivatives in moderate to good yields using O2 (1 atm) as the oxidant (Scheme 8.63). The reaction proceeds by the cleavage of the N-N bond in the N-(alkylidene)-4//-l,2,4-triazol-4-amines and activation of an aryl C(sp )-H bond in the substituted pyridines [108]. 

Jiang and coworkers developed a highly efficient synthesis of imidazo[l,2-a]pyridine derivatives from pyridine with ketone oxime esters using Cul catalyst (Scheme 8.64). The C(sp )-H bond of ketone oxime esters and C(sp )-H bond pyridinium were activated in this transformation. Air is used as the sole oxidant and HOAc and H2O are the only green by-products [109]. 

Scheme 8.64 Synthesis of imidazo[l,2-a]pyridine derivatives from pyridine with ketone oxime esters.

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