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Synlett 2008(13): 1973-1976  
DOI: 10.1055/s-2008-1077973
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Copper-Catalyzed Mild and Efficient Entry to 1-Substituted Indazolones

Shinji Tanimori*, Yuka Ozaki, Yasukazu Iesaki, Mitsunori Kirihata
Department of Bioscience and Informatics, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
Fax: +81(72)2549918; e-Mail: tanimori@bioinfo.osakafu-u.ac.jp;
Further Information

Publication History

Received 17 April 2008
Publication Date:
15 July 2008 (online)

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Abstract

A variety of 1-alkyl- and aryl-substituted indazolones were synthesized easily starting from commercially available 2-halobenzoic acids and hydrazines via the copper-catalyzed intramolecular C-N bond formation of 2-halobenzohydrazides under mild conditions.

Key words

indazolone - copper - proline - coupling - hydrazide

    References and Notes

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    Thieme Connect
13

The acid hydrazides were synthesized from corresponding acid chloride with hydrazine or the condensation of
2-halobenzoic acid with hydrazine using EDC.

18

Typical Experimental Procedure - Synthesis of 1- tert -butyl-1,2-dihydroindazol-3-one
The mixture of 2-iodobenzoic acid N′-tert-butylhydrazide (0.32 g, 1.0 mmol), CuI (19 mg, 0.10 mmol, 10 mol%), l-proline (23 mg, 0.20 mmol, 20 mol%), and K2CO3 (0.28 g, 2.0 mmol) in DMSO (10 mL) was stirred at r.t. for 3 h under nitrogen atmosphere. The mixture was treated with H2O and the mixture was extracted three times with EtOAc. The combined organic layer was washed with H2O and brine, and dried over MgSO4. After filtration, solvent was evaporated in vacuo to ca. 1 mL and crystallization afforded 1-tert-butyl-1,2-dihydroindazole-3-one (0.19 g, 97%) as white crystals. R f  = 0.36 (hexane-EtOAc, 1:1); mp 115-117 ˚C. IR (KBr): 2979 (NH), 1648 (C=O), 1538, 1209, 748 cm-¹. ¹H NMR (400 MHz, DMSO): δ = 10.47 (br s, 1 H, NH), 7.61 (d, 1 H, J = 8.5 Hz, C-4), 7.59 (d, 1 H, J = 7.8 Hz, C-7), 7.26 (dd, 1 H, J = 6.8, 8.5, Hz, C-5), 6.96 (dd, 1 H, J = 6.8, 7.8 Hz, C-6), 1.60 (s, 9 H, t-Bu). ¹³C NMR (136 MHz, DMSO): δ = 152.8, 139.5, 126.4, 120.1, 118.2, 113.9, 111.9, 58.3, 29.3 (3 × C). ESI-HRMS: m/z calcd for C11H14N2O 191.1179; found: 191.1182.

19

Acid hydrazide derived from 2,4,6-trichlorophenyl-hydrazine, tert-butylcarbazide, benzoylhydrazine, and
p-toluenesulfonylhydrazine did not afford the corresponding indazolone to recover the starting material even at heating conditions (>100 ˚C).

21

A variety of compounds possessing pharmaceutical profile have been prepared from indazolone derivatives, see ref. 15.