3-Chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione

Abstract

Abstract:The indole ring system is a prominent partial structure of several protein kinase inhibitor families. The title compound is the first example of a 5-substituted indolyl squaryl chloride with free indole nitrogen. It has been synthesized by reaction of 5-methoxyindole with squaric acid dichloride in diethyl ether and its IR, 1 H-NMR, 13 C-NMR, MS, UV and HPLC data are presented. This compound may prove to be a rather useful building block for the preparation of various derivatives for biological studies. Keywords: Friedel-Crafts acylation; indole; squaric acid dichlorideThe indole ring system is a prominent partial structure of several protein kinase inhibitor families, e.g., bisindolylmaleimides (BIMs) [1], staurosporine analogues [2], and paullones [3,4]. With the aim to develop protein kinase inhibitors based on novel scaffolds by structure-guided design methods [5] we were interested to combine the indole ring system with squaric acid derived structure elements. The latter have recently been highlighted as "unusual" chemical structures with high potential for drug development [6]. A review of the literature revealed that only few squarylated indoles are described [7][8][9]. Only a single study mentioned a 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione unsubstituted at the indole nitrogen [10]. We here report the detailed synthesis procedure of the title compound 3 as first example of a 5-substituted indolylchlorocyclobutenedione with free indole nitrogen. This compound may prove to be a rather useful building block for the preparation of various derivatives for biological studies.According to the high reactivity of the indole ring system for electrophilic attack in 3-position, the synthesis was carried out by means of a Friedel-Crafts acylation reaction from 5-methoxyindole (2) OPEN ACCESS

1-(Imidazo[1,2-a]pyridin-1-ium-1-yl)-2,3,4-trioxocyclobutan-1-ide

“…As part of our effort to find new chemotherapeutics for the treatment of malaria, we have prepared a series of bisindolylcyclobutenediones [1] according to a literature procedure [2] by Friedel-Crafts acylation of indoles with squaric acid dichloride (3). For this, we needed as starting compounds squarylated indoles, for example, 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione [3]. When we tried to extend the procedure to the reaction of 7-azaindole with squaric acid dichloride, we obtained, instead of the expected product, a pyridinium-ylide [4].…”

“…When we tried to extend the procedure to the reaction of 7-azaindole with squaric acid dichloride, we obtained, instead of the expected product, a pyridinium-ylide [4]. Because of this unexpected result, it seemed interesting to study the reaction of imidazo[1,2-a]pyridine (2) with squaric acid dichloride (3). Electrophilic substitution of 2 is expected to occur at the 3-position.…”

2,3,4-Trioxo-1-(1H-pyrrolo[2,3-b]pyridin-7-ium-7yl)-cyclobutan-1-ide

“…In addition, squaramides have a high impact in asymmetric organocatalysis [3]. With the aim to develop novel squaric acid derived structures for screening purposes, we prepared several squarylated indoles [4] according to a literature procedure [5] by Friedel-Crafts acylation of indoles with squaric acid dichloride (3), for example, 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione [6]. Upon the attempted synthesis of the squarylated 7-azaindole 4 from 7-azaindole (2) and squaric acid dichloride (3), the mesoionic title compound 1 was produced (Scheme 1).…”