followed by HCI (3 equiv. as a 1.0 M solution in anhydrous ether). The capped flask was then heated for 4 h to 100° C. After cooling, the solvent was evaporated and the residue taken up in DCM and filtered.The filtrate was purified by preparativeTLC using a gradient of 0-5 % MeOH in DCM.
Furthermore, an intramolecular nucleophilic attack is also possible and was demonstrated in the synthesis of l,4-benzodiazepine-2,5-diones  via the Ugi four-component condensation. The strategy of the convertible isonitrile was also used for the synthesis of diketopiper-azine libraries ,
By the incorporation of a furfurol aldehyde and an activated dienophile acid in the four-component reaction an intermediate 7 was formed which underwent a Diels-Alder reaction leading to tricyclic heterocycles of type 8 (Scheme 4) . The reaction was performed in solution as well as with the resin-bound amine component.
As indicated already, the initial step in the Ugi reaction is the formation of a Schiff base resulting from the aldehyde and the amine component. This Schiff base is then attacked by the isonitrile. In the Passerini reaction, the amine is omitted so that the isonitrile reacts directly with the carbonyl function of the aldehyde which yields compounds of type 9  (Scheme 5).
The reaction was applied in solution to create an array of azinomycin analogs, a class of antitumor compounds which bind to the major groove of double-stranded DNA and which leads to crosslinking of the two complementary single strands [9,10]. In the same publication, the Passerini reaction contemplating azinomycin analogs was performed on a solid support whereby the acid component was attached before the synthesis via a photolabile linker to the solid support .
The diversity possibilities of multicomponent reactions can be further increased by prior functionalization of one of the components. This strategy, also dubbed "reagent explosion", was recently employed in a Passerini reaction in which methyl-P-(N,N-dialkylamino)-oc-
isocyanoacrylates 10 were introduced as isocyanide component  (Scheme 6). The iso-cyanide derivatives were easily prepared from the reaction between various secondary amines, N-formylimidazole diethylacetal, and methyl isocyanoacetate as outlined in Scheme 6. Dipolar aprotic solvents such as dimethylformamide (DMF) and dimethylsulfoxide (DMSO) were found to be superior in this multicomponent reaction, whereas the commonly applied methanol was not suitable. The authors have used this reagent explosion strategy for the synthesis of a 4620-member library consisting of compounds of type 11.
Methyl-(3-(N,N dialkylamino)-a-isocyanoacrylates of structure 10 were also applied in a Ugi reaction in which the commonly used carboxylic acid component was replaced by hy-drazoic acid . This resulted in the formation of interesting bicyclic tetrazole derivatives 12, as outlined in Scheme 7.
R1CHO + R3NC + R4COOH Scheme 5
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