Hexahydrospiro‐pyrazolo[3,4‐b]pyridine‐4,1′‐pyrrolo[3,2,1‐ij]quinolines Derived from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione

Abstract

The tricyclic isatin, 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione (1), reacts with a combination of an aryl cyanomethyl ketone 8 and a 5‐amino‐1‐arylpyrazole 7 to generate spirocyclic products 9.

Synthesis of Hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1′‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones] from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione Using Fe3O4@Cu(OH)x as a Nanocatalyst

“…As discussed in Introduction section, these three‐component combinations could possibly proceed by one of two routes: reaction of the amido‐ketone 1 with the pyrazole‐5‐amine 6 as a first step or reaction of 1 with the cyclohexane‐1,3‐dione 12 as a first step. Using the nanocatalyst, we prepared the condensation product 10 , utilized in our previous study . It was shown to react very efficiently with dimedone ( 12 , R 1 = 5,5‐Me 2 ) to form the spiro product 13j , identical to that prepared using the three‐component protocol (Scheme ).…”

“…After completion of the reaction in 15 h (monitored by TLC, silica, EtOAc/hexane, 1:2), the mixture was cooled to RT, the nanocatalyst was separated by an external magnet, and then H 2 O (10 mL) was added. The resulting precipitate was filtered off and washed with H 2 O (10 mL), and the crude powder was recrystallized from EtOH to give white crystals, 91% yield, mp 256–258°C identical spectroscopically to that prepared previously using TsOH as catalyst.…”

“…Instead, we showed that the isatin 1 reacts with a typical 5‐aminopyrazole 9 producing 10 , in which the electrophilic ketone has alkylated the pyrazole 4‐position, and that this compound did react with a cyanomethyl ketone to form a spiro product 11 (Scheme ) .…”

“…We have previously described the synthesis of spiro[3,3′‐oxindoles] beginning from 5,6‐dihydro‐4 H ‐pyrrolo[3,2,1‐ ij ]quinoline‐1,2‐dione ( 1 ) , which is a tricyclic analogue of isatin (1 H ‐indole‐2,3‐dione). The synthetic strategy relies on the high reactivity of the ketone carbonyl group of the isatin.…”

“…In our most recent exploitation of the strategy discussed above, we showed that 1 reacts in a three‐component one‐pot process with cyanomethyl aryl ketones 5 and 5‐amino‐1‐aryl‐3‐methylpyrazoles(1‐aryl‐3‐methylpyrazole‐5‐amines) 6 to generate spiro products 7 (Scheme ) .…”