Synthesis of pyrazole‐fused azepino[5,4,3‐cd]indoles

Abstract

The synthesis of some new pyrazolo [3',4':6,7]azepino [5,4,3-cd]indoles (10a-c) was achieved via regioselective cyclization of the respective 3-(4-acylaminopyrazol-5-yl)indoles (9a-c) under Bischler-Napieralski reaction conditions. The latter compounds were obtained by acylation of the corresponding 3-(4-aminopyrazol-5-yl)indoles (8a,b) which, in turn, were prepared by reduction of the 3-(4-nitropyrazol-5-yl)indoles precursors (7a,b). The latter synthons were accessible from the reaction of indolylzinc chlorides (5a,b) with 5-chloro-1,3-dimethyl-4-nitropyrazole. Ms and nmr spectral data of 10a-c are in agreement with the assigned azepino-indole structure as determined for 10a by X-ray crystal measurements which demonstrate that the azepine ring is almost completely planar with the indole and pyrazole rings.

Synthesis of Some Thiophene-fused Azepino[5,4,3-cd]indoles

“…The required 3-(3-nitrothien-2-yl)indole 7is readily prepared via coupling of indolylzinc chloride (5) with 2-chloro-3-nitrothiophene (6) (Scheme 1), following similar procedure previously reported for 3-(4nitropyrazol-3-yl) indoles 16 and related 3-(heteroaryl)indoles. 18 Reduction of 7, using tin and hydrochloric acid in the conventional manner, yielded the respective 3-(3-aminothien-2-yl)indole (8) characterized as its monohydrochloride salt.…”

“…In this respect, compounds ( 9a-c ) behaved in a similar manner to their 3-(4-aminoacylpyrazol-3-yl)indole analogs which were reported to cyclize into pyrazoloazepino [5,4,3-cd]indoles. 16…”

“…receptor ligands, 13 useful for treatment of circulatory and digestive tract disorders, 14 as psychotropics, 14 diuretics and smooth muscle relaxants. 15 As part of our work concerning the synthesis of fused heterocycles with potential therapeutic interest, we have described some pyrazoloazepino [5,4,3-cd]indoles 16 and pyrazolo-β-carbolines. 17 In continuation, we thought it is worthwhile to prepare the tetracyclic system 3incorporating both thienoazepine (1) and azepinoindole (2) moieties.…”

Green Cyclocondensation of β-Ethylthio-β-indolyl-α, β-unsaturated Ketones with Semicarbazide Hydrochloride as Hydrazine Equivalent in Water: Aqueous Synthesis of 3-Pyrazolyl Indoles

“…3-Pyrazolyl indoles as an important subset of 2 indole derivatives had exhibited their versatile synthetic values [3][4][5][6][7] and a broad spectrum of biological activities [8][9][10] such as antimicrobial 11 , anti-inflammatory 12 and antioxidant 13,14 . As a result, much effort has focused on the synthesis of 3-pyrazolyl indoles, mainly including the cyclocondensation of 1, 3-diketones and related derivatives with hydrazines [15][16][17][18][19][20][21][22] , the direct coupling of indole derivatives and pyrazole derivatives 23,24 , acid-catalyzed intramolecular cyclization reaction of N-propargylation of N-acetyl-N-tosyl-hydrazine 25 , and other procedures [26][27][28] . However, all the reported reactions are performed in organic medium and extremely toxic hydrazines appear as a main nitrogen source for most of reactions, which can lead to serious environmental and safety problems.…”