Amination of 5-Spiro-Substituted 3-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones

Abstract

The 3-hydroxy-1,5-dihydro-2H-pyrrol-2-one motif is a valuable scaffold in drug discovery. The replacement of the 3-oxy fragment in 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones-based compounds with a 3-amino one (3-amino analogs of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, 3-amino-1,5-dihydro-2H-pyrrol-2-ones) can play a crucial role in their biological effect. Thus, approaches to 3-amino-1,5-dihydro-2H-pyrrol-2-ones are of significant interest. We developed an approach to 5-spiro-substituted 3-amino-1,5-dihydro-2H-pyrrol-2-ones that could not be obtained using previously reported approaches (reactions of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones with amines). The developed approach is based on the thermal decomposition of 1,3-disubstituted urea derivatives of 5-spiro-substituted 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, which were prepared via their reaction with carbodiimides.

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

“…Noteworthy, we had to derivatize product 3aa to detect it by HPLC–UV during the optimization studies. For these purposes, compound 3aa was converted to compound 4 by an earlier procedure developed by us ( Scheme 7 ) [ 51 ]. Without this derivatization procedure, we could not accurately detect compound 3aa by HPLC–UV, since the chromatographic signals of untreated compound 3aa were broad and blurry.…”

“…As in the cases of the above studied reactions ( Scheme 7 , Scheme 12 ), we had to derivatize the product 12aa ( Scheme 17 ) by an earlier procedure developed by us [ 51 ] in order to investigate the reaction optimization by HPLC-UV.…”