RhIII/CuII-Cocatalyzed Synthesis of 1H-Indazoles through C–H Amidation and N–N Bond Formation (original) (raw)

Efficient Synthesis of 7-Substituted or 3,7-Disubstituted 1H-Indazoles

Synlett, 2007

This work reports on the synthesis of the novel indazole scaffolds 7-OTf-1H-indazole (trifluoromethanesulfonic acid 1Hindazol-7-yl ester), 7-iodo-1H-indazole and 3-bromo-7-iodo-1Hindazole. These new compounds are potent building blocks in divergent syntheses of indazoles via palladium cross-coupling reactions.

Efficient Synthesis of 7-Substituted or 3,7-Disubstituted 1 H -Indazoles

Synlett, 2007

Abstract: This work reports on the synthesis of the novel indazole scaffolds 7-OTf-1H-indazole (trifluoromethanesulfonic acid 1Hindazol-7-yl ester), 7-iodo-1H-indazole and 3-bromo-7-iodo-1Hindazole. These new compounds are potent building blocks in divergent syntheses of indazoles via palladium cross-coupling reactions.

A Versatile Synthesis of Substituted Indazoles

HETEROCYCLES, 1995

A four-step synthetic sequence for substituted indazoles was presented from 2-acylcyclohexane-1.3-diones via either simultaneous or stepwise dehydration and dehydrogenation of 4-substituted 4-hydroxy-4.5.6.7tetrahydroindazoles as a key step. The synthetic methods for indazole nucleus are somewhat limited to involve condensation of hydrazino group,' generated by in situ reduction of diazo group in c-diazophenyl ketones, with C-0 of the substi tuent at the neighboring posi tion, and dehydrogenation of 4.5,6,7-tetrahydroindazoles. The former method, however, is suffering from low yields, limitations of employable diazophenyl ketone^,^ explosive intermediates.' and the latter method is also suffering from extreme reaction conditions5 as well as low yields.' Other methods have been reported, but so far not so effective to overcome the limitations of introducing substituent on indazole skeletons, especially at C3 and/or ~4 .~ In the present paper, we describe a facile and efficient route for the preparation of indazoles, in which substituents can be easily introduced at C3 andlor Ca. RESULTS AND DISCUSSION Our strategy stems from the idea that the introduction of a proper leaving group on the tetrahydroindazole system may affect the dehydrogenation step. Upon this rationale, 4-hydroxy-4.5,6.7-tetrahydroindazoles were selected as key intermediates, which may readily undergo either stepwise or simultaneous dehydration and dehydrogenation. The synthetic sequence is, thus, quite straightforward as shown in Scheme I. The prerequisite 2-acylcyclohexane-1.3-diones (1) were prepared by previously reported methods either direct acylation7 of cyclohexane-1.3-dione or via Fries rearrangements of 3-acylow-2-cyclohexenones9 in 88.92% yields. The latter procedure gave better yields, 8 as reported. It is worthy to note that I3c nmr spectral data provided information for the enol-keto tautomerism on 2-acylcyclohexane-1.3-diones. The presence of one sp2 carbon resonance (6 112.0) and three carbonyl resonances at 6 194.9. 199.0, and 210.3 implies that keto form is the major component in compound (la) on the "C nmr scale. In the system with aromatic ring, compound (lb), however, four 2 additional sp carbon resonances appeared at 6 127.5. 128.1. 131.9. 134.2 with disappearance of the two sp3 carbon resonances at 6 32.1. and 37.9, representing G and Cs, respectively. and one carbonyl resonance was shown at 6 198.7. This impies that enol form is the major component in compound (Ib). On

Synthesis of Novel Substituted Indazoles via Nucleophilic Substitution of Hydrogen

New four-substituted indazoles 4a-e were synthesized by regioselective nucleophilic substitution of hydrogen of N-alkyl-7-nitroindazoles 2a,b with arylacetonitriles 3a-c. Compounds 4a-e were reacted with arylsulfonyl chloride in pyridine to give some new indazole linked sulfonamides with good yields. The S N H at position C-4 of 7-nitroindazole with arylacetonitrile is confirmed by X-ray diffraction analysis of compounds 4e and 6a. C 2015 Wiley Periodicals, Inc. Heteroatom Chem. 26:374-381, 2015; View this article online at wileyonlinelibrary.com.

Efficient synthesis of new 3-heteroaryl-1-functionalized 1H-indazoles

Tetrahedron, 2011

The efficient synthesis of novel 3-heteroaryl N-1-functionalized indazoles, via palladium cross-coupling reactions of ethyl (3-iodo-1H-indazol-1-yl)acetate with 2-and 3-pyrrolylboronic acids, 2-, 4-and 5-thiazolylstannanes, and other heteroarylmetallated derivatives are reported.

An efficient synthesis of 1- H indazoles

Tetrahedron Letters, 2007

The reaction of substituted salicyaldehydes with hydrazine hydrochloride under different conditions gave the corresponding 1-H indazoles. However, the reaction of benzaldehydes with hydrazine hydrate under the same conditions yielded only hydrazones.

A novel and efficient synthesis of 3-aminomethyl-N-tosyl-indazoles

Tetrahedron, 2010

A practical and environmentally friendly synthesis of 3-aminomethyl-N-tosyl-indazoles is developed. The in situ formed vinyl azines are reacted with amines to furnish amino functionalized anti-hydrazones in excellent yields. Subsequent copper-catalyzed cyclization at ambient temperature is effective and desired compounds are obtained in short reaction times. Also, the formation of bisindazoles is presented for the first time.