4- Amino-1 //-imidazo pyridine

Almost accidentally, Bienayme and Bouzid discovered that heterocyclic amidines 9-76 as 2-amino-pyridines and 2-amino-pyrimidines can participate in an acid-catalyzed three-component reachon with aldehydes and isocyanides, providing 3-amino-imidazo[l,2-a]pyridines as well as the corresponding pyrimidines and related compounds 9-78 (Scheme 9.15) [55]. In this reachon, electron-rich or -poor (hetero)aromatic and even sterically hindered aliphatic aldehydes can be used with good results. A reasonable rahonale for the formation of 9-78 involves a non-con-certed [4+1] cycloaddition between the isocyanide and the intermediate iminium ion 9-77, followed by a [1,3] hydride shift. 

Aminoimidazo[4,5-6]pyridines (317) may be prepared in a two-step procedure (Scheme 31). Acylation of 2,3-diaminopyridine (315) with ethoxycarbonylisothiocyanate in the presence of tri-ethylamine gives a mixture of l-(2- and 3-methoxycarbonyl)-3-pyridinylthioureas (316) which upon treatment with DCC cyclize to give the 2-ethoxycarbonylamino derivative (317). The 2-amino-imidazo[4,5-b]pyridine (318) was prepared in 38% yield by the hydrolysis of the ester (317) with 4 M NaOH. 

The reaction has been recently utilized to prepare functionalized 3-amino-imidazo[l,2-a]pyridines from aldehydes, 2-aminopyridines and isocyanides, as shown in Scheme 3 [17]. 

Amino-imidazo[l,2-fl]pyridines exist as amino tautomers, but are even more unstable than amino-indolizines. 2- and 5-oxo compounds are in the carbonyl tautomeric form and react with phosphoryl chloride yielding chloro compounds. ... 

IP 166 with a somewhat unusual structure formed in good yield when 3-amino-imidazo[l,2-a]pyridine 165 was condensed with acetylacetone, the former playing the part of a 4-aminoimidazole derivative (94H1527). 

Pyrido[2,3-d]imidazo[2,l-b]thiazolo[5y4-b]pyridine (CsNS-CsNi-CsN-CsN) and Related Systems.—The readily available 2-chIoro-3-isothiocyanatopyridine (284) reacts with compounds containing both electrophilic and nucleophilic centres to form a variety of condensed thiazolopyridines. Its interaction with aminoacetonitrile, for example, furnishes 56% yields of 1-amino-imidazo[2,l-b]thiazolo[5,4-b]pyridine (285). Its condensation with methyl-... 

Imidazo[l,2-n]pyridine, 8-amino-synthesis, 5, 631 Imidazo[l,2-n]pyridine, 3-aryl-synthesis, 5, 631-632 Imidazo[l,2-n]pyridine, 3-bromo-synthesis, 5, 631... 

Imidazo[4,5-6]pyridine, 2-acetonyl-3-phenyl-synthesis, 5, 637 Imidazo[4,5-6]pyridine, amino-acylation, 5, 619... 

Imidazo[4,5-6]pyridine, 7-amino-4-(tri-0-benzoyl-jS-D-ribofuranosyl)-synthesis, 5, 615... 

Imidazo[4,5-c]pyridine, 6-amino-4-bromo-reactions, 5, 621 synthesis, 5, 641... 

Imidazo[4,5-c]pyridine, 4-amino-6-chloro-l-jS- D-ribofuranosyl-hydrogenation, 5, 621... 

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. 

Aldehydes and the corresponding 2-aminopyridine, pyrazine, or pyrimidine are admixed in presence of a catalytic amount of clay (50 mg) to generate iminium intermediate. Isocyanides are subsequently added to the same container and the reactants are further exposed to MW to afford the corresponding imidazo[l,2-a]pyridines, imi-dazo[l,2-a]pyrazines and imidazo[l,2-a]pyrimidines (Scheme 6.48). The process is general for all the three components, e. g. aldehydes (aliphatic, aromatic and vinylic), isocyanides (aliphatic, aromatic and cyclic) and amines (2-aminopyridine, 2-amino-pyrazine and 2-aminopyrimidine). A library of imidazo[l,2-a]pyridines, imidazo[l,2-ajpyrazines and imidazo[l,2-a]pyrimidines can be readily obtained by varying the three components [151]. 

The addition-elimination adducts (143)-(145) are also useful precursors to imidazo[4,5-b]pyridines. Thus, the malonate derived products (143) on treatment with hot ethanolic HC1 [92JCS(P1)2789] or hot ethanolic triethylamine (78H241) gave the imidazo[4,5-b]pyridones (157). The dinitrile derivatives (144) gave the ortho amino nitriles (158) by treatment with hot methanolic sodium hydroxide solution and the nitrile esters (145)... 

Compound 642, obtained by condensation of glyoxal with benzotriazole and morpholine undergoes interesting [2+3] cyclocondensation with 2-aminopyridine to give imidazo[l,2- ]pyridine 643 (Equation 15) <2003JOC4935>. Similar derivatives of piperidine and pyrrolidine are also described. 2-Amino- and 6-aminopyrimidines react similarly to give imidazo[l,2- ]- and imidazoll - pyrimidines, respectively. 

A Vilsmeier reaction of pyridine-2-carbonitriles 126 was found to produce mixtures of l-formyl-2-dimethyl-amino[l,5-4]pyridines with a chlorine atom 127 or a hydrogen 128 at the C-7 position < 1998J(P 1 )3851 >. When extended to isoquinoline-1 -carbonitriles such as 129, this reaction gave in modest yield compounds 130 (Scheme 40). Later on, it was demonstrated that this reaction leads to imidazo[l,5- ]pyridinium chlorides when A,A-dimethylbenzamides were used instead of dimethylformamide (DMF) <1999H(50)887>. 

Amino-2,3-dimethyl-3//-imidazo[4,5-fc]pyridine was reacted with EMME in boiling toluene for 2 hr to afford 7V-(imidazopyridin-5-yl)amino-methylenemalonate (91) in 84% yield (86EUP174832). The reaction of 3-amino-4,6-dimethyl- l//-pyrazolo[3,4-6]pyridine and EMME yielded N-(4,6- dimethyl -1 //- pyrazolo[3,4 - 6]py ridin- 3 - y l)aminomet hy lenemalonate (92) (87MI5). 

Z-aminO 1 -methy 1 6 phenylimidazo [4,5-b]-pyridine 2 aminO 3,7,8 trimethylimidazo[4,5 f]quinoxaline 2 aminO 3,4,7,8 tetramethyl 3H imidazO [4,5 f]quinoxaline inoxaline 3 aminO l,4 dimethyl SH pyrid [4,3 b] indole (Trp P I) and 3 aminO l methyl 5H pyrido [4,3 b]indole induced mutagenesis. Metabolic activation was required for positive results b... 

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