6- Aminoimidazo pyridines

Both 5- and 7-amino derivatives of 133 were diazotized and converted into the chloro derivatives using concentrated hydrochloric acid with or without copper(I) chloride (72RTC650 78JHC839). Similarly prepared from 4-aminoimidazo[4,5-c]pyridine was the 4-chloro derivative (65JMC708). A nitro group in the 4-position of 134 was particularly susceptible to nucleophilic displacement by halide (74CHE744). 

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. 

A library of biologically relevant 2-aryl-3-aminoimidazo[l,2-fl]pyridines and 2-aryl-3-aminoimidazo[l,2-fl]pyrazines was created using a combina-... 

Blackburn, C. Guan, B. Fleming, P. Shiosaki, K. Tsai, S. Parallel Synthesis of 3-Aminoimidazo[l,2-a]pyridines and Pyrazines by a New Three-Component Condensation, Tetrahedron Lett. 1998, 39, 3635. 

Groebke, K., Weber, L. and Mehlin, E, Synthesis ofimidazo[l,2-a] annulated pyridines, pyrazines and pyrimidines by a novel three-component condensation, Synlett, 1998, 661 Blackburn, C., Guan, B., Shiosaki, K. and Tsai, S., Parallel synthesis of 3-aminoimidazo[l,2-a] pyridines and pyrazines by a new three-component condensation, Tetrahedron, 1998, 3635-3638 Bienayme, H. and Bouzid, K., A new heterocyclic multicomponent reaction for the combinatorial synthesis of fused 3-aminoimidazoles, Angew. Chem., Int. Ed. Engl, 1998, 37, 2234-2237. 

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 same group reported on a library synthesis of 3-aminoimidazo[l,2-a]-pyridines/pyrazines by fluorous multicomponent reactions. Here the overall yields, as well as the yields for the separate Suzuki-Miyaura reactions that were a part of the synthesis, were relatively low due to competing reactions and the poor reactivities of the substrates, but the speed of the microwave-mediated syntheses and ease of separation underlined the usefulness of fluorous reagents [140]. A recent paper further illustrated the use of Suzuki-Miyaura couplings of aryl perfluorooctylsulfonates in the decoration of products derived from 1,3-dipolar cycloadditions [141]. 

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

Diazotization of the 4-aminoimidazo[4,5-Z>]pyridine (245) in concentrated hydrochloric acid furnishes the 4-chloro derivative (246) <87JMC1746>. 

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. 

Rearrangement of alkoxycarbonyl imidazole acryl azides in diphenyl ether at high temperatures afforded imidazo[l,5-c]pyrimidinone or imidazo[4,5-c]pyridinone derivatives <02TL5879>. Efficient synthesis of imidazopyridodiazepines from peri annulation in imidazo[l,2-a]pyridine has been described <02TL9119>. A convenient synthesis of 3,6-disubstituted-2-aminoimidazo[l, 2-a]pyridines has been published <02TL9051>. Novel 2,3-dihydroimidazo[2,l-h][l,3]oxazoles were prepared from intramolecular nucleophilic i/wo-substitution of 2-alkylsulfonylimidazoles <02S2691>. 4,4 -Bi-l//-imidazol-2-ones were efficiently synthesized from 5-amino-ot-imino-1 //-imidazole-4-acetonitriles and isocyanates <02JOC5546>. 

Both Siegel et al. (122) and Lawrence et al. (123) have described automated systems for the purification of small arrays of amines and amides. A 48-member array of P-amino alcohols prepared from epoxides and amines was purified using SPE by Shuker et al. (124). Blackburn et al. (125) have described the purification of a 60-member 3-aminoimidazo[l,2-fl]pyridine array obtained from a multiple-component condensation, and Bussolari et al. (126) purified a small array of phenylpropyl amines obtained from dihydrocoumarins and amines. A few applications where ion-exchange resins have been substituted with other solid phases have also recently appeared. For example, the purification of several carbohydrate arrays tagged as hydrophobic O-laurates using Ci8 silica producing up to 10-30 mg of >90% pure individuals was described by Nilsson et al. (127), and Curran et al. purified fluorous-... 

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... 

Several 6-aminoimidazo[l,2-a]pyridines were prepared from 6-iodoimidazo[l,2-a]pyridines via copper- and palladium-catalyzed aminations <03JOC4367>. 

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>. 

Reduction of l-/3-D-ribofuranosyl-4-hydrazinoimidazo[4,5-c]pyridine (173) with Raney nickel cleaved the N—N bond in typical fashion to give the adenosine analog 4-amino-l-/8-D-ribofuranosylimidazo[4,5-c]pyridine (174) (66B756), whereas l-aminoimidazo[4,5-... 

Refluxing ethyl 2-(3-aminopyridin-4-yl)hydrazinecarboxylate (419) in 36% methanolic hydrogen chloride for 8 hours gave l-aminoimidazo[4,5-c]pyridin-2(3i/)one hydrochloride (423), rather than the expected pyridotriazinone (420), thought to be an intermediate in the formation of (423) via (421) and (422) (76JHC601). 

Multicomponent reactions have been described for several syntheses of imidazoles. Highly efficient methods for the syntheses of spiroimidazolinones via microwave-assisted three-component one-pot sequential reactions or one-pot domino reactions have been described <06JOC3137>. Multicomponent reactions between 2-aminopyrimidine, aldehydes and isonitriles afforded imidazo[l,2-a]pyrimidines <06TL947>. Two novel one-step microwave mediated syntheses of arrays of 3-iminoaryl-imidazo[l,2-a]pyridines and imidazo[l,2-a]pyridyn-3-ylamino-2-acetonitriles were synthesized by multicomponent reactions under microwave condition in methanol by simply mixing a-aminopyridines, aldehydes, and trimethylsilylcyanide catalyzed by polymer-bound scandium triflate <06TL2989>. 3-Aminoimidazo[l,2-a]pyridines have been synthesized via the multicomponent reaction of aldehydes, isocyanides and 2-aminopyridines in the presence of the ionic liquid l-butyl-3-methylimidazolium bromide [bmim]Br<06TL3031>. 

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