5- Aminoimidazo pyridine, reaction with

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. 

The time consuming chromatographical purification of heterocycles 28 and 29 slowed down the rate of library production. A phase separation using fluorous chemistry was employed by Zhang and Lu to address the workup and purification of fused 3-aminoimidazo[ l,2-a]pyridines (such as 30) [54]. Thus, attachment of a perfluorooctanesulfonyl tag to aldehydes and subsequent Ugi three-component microwave-assisted condensations with 2-aminopyridines and isocyanides furnished the desired heterocycles 30, which were conveniently isolated by fluorous solid-phase extraction. The fluorous tag could be subsequently used as an activating group in the post-condensation modifications, such as Suzuki-Miyaura cross-coupling reactions. 

The reaction of the derivatives (147) with O-mesitylenesulfonylhydroxylamine in methanol affords 5-aminoimidazo[4,5-c]pyridine (148) (Equation (6)) <86T1511>. 

Similarly, a novel one-pot microwave-assisted reaction has been described by Hulme and co-workers that enables the selective formation of 3-iminoaryl-imidazo[l,2-a]pyridines 19 and imidazo[l,2-a]pyridyn-3-ylamino-2-acetonitriles 20, in good yields. Reactions were performed in methanol by mixing a suitable a-aminopyridine, an aldehyde and trimethylsilylcyanide (TMSCN) with polymer-bound scandium triflate, to afford either product 19 or 20 (Scheme 16). Initially, the 3-iminoaryl-imidazo[l,2-a]pyridine 19, was observed as a minor side product (0-10%) during the pseudo-Ugi reaction affording the 3-aminoimidazo[l,2-a]pyridine 18. However, by increasing the aldehyde input to 2.2 equiv the reaction could be directed to the formation of 19 in moderate yields. Interestingly, low yields of... 

A series of 3-aminoimidazo[ 1,2-a]pyridines were synthesized by the reaction of substituted pyridines with l,2-bis(benzotriazolyl)-l,2-(dialkylamino)ethanes <03JOC4935>. 

Aminopyridines can be used in other ways copper-catalysed interaction with diazo-ketones and three-component reactions involving an isonitrile and an aldehyde also give imidazo[l,2-a]pyridines such condensations can be promoted using an ionic liquid" or scandium triflate with microwave heating." In the former route, 2-substituted products result and from the latter, 3-aminoimidazo[l,2-a]pyridines are formed. 

The formation of pyridine IV-imines by an add-catalyzed rearrangement of some diazepinones and related compounds has been extensively investigated by Moore and co-workers (Eq. 9).115 The formation of pyridine N-imines from l/f-l,2-diazepines is also known (Eq. 10).68 69,116,117 Diels-Alder reactions of pyrazoles with dimethyl acetylenedicarboxylate, in the presence of BF3, have been reported to give IV-aminopyridinium salts (Eq. II).118 l,4-Dihydropyrido[l,2-a]-as-triazinium salts and their pyrimido derivatives undergo ring contraction in boiling aqueous acid, yielding 1-aminoimidazo[l,2-a]pyridinium and pyrimidinium salts, respectively (Eq. 

A catalyst-free protocol has been described by Adib for the synthesis in good to excellent yields of 3-aminoimidazo[l,2-o]pyridines and 5-aminoimidazo[2,l-6] [l,3]thiazoles via three-component reactions between 2-aminopyridines or 2-ami-nothiazoles, aldehydes and isocyanides in water (Scheme 1.10) [14]. Presumably, this process involves the initial formation of an imine, which then reacts with the isonitrile in a formal [4+2] cycloaddition. 

Typically, these heterocycles are synthesized by the cyclocondensation of 2-aminopyrimidine with a suitable R-bromoacetophenone in polar solvents [129-131]. Shaabani et al. reported a three-component condensation reaction of aldehydes, 2-amino-5-methyl-[Br]pyridines, and isocyanides to afford 3-aminoimidazo[l,2-fl]pyridines 65 in good yield (Scheme 25) at RT in the presence of [BMlM][Br] in a molar ratio of 1 1.4 (reactant/IL) [132]. In the absence of IL, the yield of 65 could not exceed beyond 25% at RT even after 12 h, which established [BMIM][Br] as an essential component of the reaction. On four times recycling and reuse of IL, a gradual decrease in the yield of 65 (95%, 92%,... 

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