On the reaction of 2-[(4-cyano-5,6,7,8-tetrahydroisoquinolin-3-yl)oxy]acetamides with bases: 1-amino-6,7,8,9-tetrahydrofuro[2,3-c]isoquinoline-2-carboxamides and 3-amino-4-cyano-5,6,7,8-tetrahydroisoquinolines via a Smiles-type rearrangement

New Methods for the Synthesis of 3‐Amino‐6,7‐Dihydro‐5H‐Cyclopenta[c]Pyridine‐4‐Carbonitriles and Cyclopenta[d]Pyrazolo[3,4‐b]Pyridines via a Smiles‐type Rearrangement

“…In fact the presence of an alkoxyacetamide group (containing a potential nitrogen nucleophilic center, that could be further activated by sodium ethoxide, and at the same time of an oxygen atom, of ether type, potential leaving group) in a substrate strongly activated towards aromatic nucleophilic substitutions (a nitrogen pyridine atom and a cyano group are present) rendered possible Smiles rearrangements . The mechanism of this rearrangement is well known and has been recalled in our previous paper . It easily occurred in both benzene and heterocyclic derivatives activated to S N Ar processes, furnishing an interesting method for introducing new functionalities in aromatic systems (Scheme ).…”

“…Very interestingly, by applying the same kind of procedure to some 2‐[(1‐alkyl(aryl)‐4‐cyano‐5,6,7, 8‐tetrahydroisoquinolin‐3‐yl)oxy]acetamides 3 , we have observed that these substrates could give as a function of their structure, the ‘expected’ furo[2,3‐c]isoquinoline‐2‐carboxamides 4 , with very high yields, but also the ‘unexpected’ 3‐amino‐4‐cyano‐5,6,7,8‐tetrahydroisoquinolines 5 via a Smiles‐type rearrangement (Scheme ) depending on the structure of the amide group .…”

“…Therefore, there is a growing interest in synthetic methodologies that could give facile and reliable accesses to this class of compounds . In this research line, we have reported a synthetic procedure for the preparation of condensed ethyl 5‐alkyl(aryl)‐1‐amino‐6,7,8,9‐tetrahydrofuro[2,3‐ c ]isoquinoline‐2‐carboxylates 2 from ethyl [(1‐alkyl(aryl)‐4‐cyano‐5,6,7,8‐tetrahydroisoquinolin‐3‐yl)oxy]acetates 1 by the action of sodium ethoxide (Scheme ) .…”

“…The first reaction pathway was characteristic for amides deriving from aliphatic secondary amines or from aromatic amines; the second occurred only with amides deriving from aliphatic primary amines .…”

Efficient Syntheses of 1,2,3-Triazoloamide Derivatives Using Solid- and Solution-Phase Synthetic Approaches

“…The chloroamides 15 [31][32][33][34][35][36][37] were prepared from the reaction of secondary amines 14 (the first diversity elements R 1 and R 2 ; Figure 6) and chloro-acid chlorides 6a and 6c (the second diversity element A; see Figure 3) with triethylamine in CH2Cl2 at room temperature (99%-92% yields). Followed by SN2 reaction of tertiary amides 15 with sodium azide to generated the corresponding azidoamides 16 [15,17,[38][39][40][41] in high yields (99%-94% yields) ( Figure 7).…”