Indazole synthesis

In indazoles there are two possibilities for ring closure by creation of an N—C bond, depending on whether the bond is the N(2)—C(3) or the N(l)—C(7a) bond. Both are classical methods of indazole synthesis (types A and C (67HC(22)l)). An example of each class is shown in Scheme 50 (78S633). 

Pyrido[ 1, 2 1,2]imidazo[4,5-b]quinoxaline nomenclature, 1, 22 2,2 -Pyridoin synthesis, 2, 337 Pyrido[ 1,2-6]indazoles synthesis, 5, 335 E ridoindoles rearrangement, 4, 508 Pyrido[a]indoles synthesis, 4, 233 Pyrido[6]indoles nomenclature, 4, 498 Pyridooxadiazolones ring contraction, 4, 149... 

The most important intramolecular C-coupling reaction is the synthesis of 4,5-benzo-pyrazoles, originally called indazoles (6.70), as shown in Scheme 6-47. The indazole synthesis was discovered by Witt et al. (1890). Nolting (1904) investigated which substituted 2-methylbenzenediazonium salts yield indazoles (review Behr, 1967). 

Evidence for the diazonium acetate ion pair 6.74 was given by Barben and Suschitzky (1960) and by Suschitzky (1967). In the indazole synthesis from Af-(4-fluoro-2-tolyl)-... 

This elucidation of the mechanism of the indazole synthesis also led to a simplified Jacobson method with higher yields (Riichardt and Hassmann, 1980). In this version, 1.5 equivalents of 2-pentylnitrite are added slowly to a boiling solution of 1.0 equivalent of 2-methylaniline in benzene, 3 equivalents of acetic anhydride, and 1 equivalent of water-free potassium acetate, and the whole stirred under reflux for... 

The reaction conditions of this modified indazole synthesis can also be applied to the preparation of 1,2-diazanaphthalenes, the so-called cinnolines, although in such syntheses no deprotonation prior to cyclization is likely to occur. Ruchardt and Hassmann (1980) obtained 4-phenylcinnoline (6.85) in 53% yield from 2-(a-methyl-ene-benzyl)aniline (Scheme 6-53). 

Imidazolone synthesis, 291 Imidoline, 259 Imipramine, 420 Indapamide, 349 Indazole synthesis, 350 Indoles, as starting material for benzodiazepines, 405 Indomethacin, 345 Indoramin, 344 Incfoxoie, 254, 340 Inflammation, 63 Influenza A, 18 Inhibition,... 

Yan B, Gstach H, An indazole synthesis on solid phase support monitored by single bead FT-IR microspectroscopy, 37(46) 8325—8328, 1996. 

Bose applied Cadogan s indazole synthesis and achieved an enhanced greener one-pot process using microwave. Thus Schiff base 24 was prepared by microwaving (400 W) a mixture of equivalent amounts of the aldehyde and the aniline. The Cadogan reaction was completed imder microwave as soon as the temperature reached 150 "C with excess of triethyl phosphate to afford indazole 25. 

Figure 4.28 A cross-section of results for Rh-catalyzed Indazole synthesis by C-H bond functionalization and cyclative capture as reported by Bergman s and Ellman s groups [60].

Yan, B. and Gstach, H., An indazole synthesis on solid support monitored by single bead FTIR microspectrocopy. Tetrahedron Lett., 37 (1996) 8325-8328. 

Scheme 10.13 Indazole synthesis through Cp Co "-catalyzed C-H functionaliza-tion/dehydrative cyclization of azobenzene and aldehyde.

Scheme 16.43 C-H arylation of indazoles synthesis of YD-3, YC-1, and nigellidine hydrobromide.

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