2-H-indazoles

The 3- or 5-aminopyrazoles are the synthons used most frequently. The second heterocyclic ring is created between the amino group and the 1-position (if unsubstituted) or between the amino group and the 4-position. Thus 3-substituted 5-aminopyrazoles react with 1,3-difunctional compounds to afford pyrazolo[l,5-a]pyrimidine derivatives (538) (Table 34). Aminopyrazolinones (R = OH) can be used instead of aminopyrazoles. Similarly 3-aminoin-dazole yields pyrimido[l,2-h]indazoles (539). 

As reported by Steel et al. three structural isomers of bis(camphor-pyrazol-l-yl)methane (21a, 21b and 21c) are formed by coupling of camphorpyrazole 10 [i.e., (4S,7i )-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-l(2)H-indazole] with CH2CI2 (121). Isomer 21c can be separated from the other two structural isomers by crystallization or column chomatography. Deprotonation at the bridging carbon atom, subsequent reaction with carbon dioxide and acidic workup yields the enantiopure bis(camphorpyrazol-l-yl)acetic acid Hbpa (8) (Scheme 17, Fig. 19) (116). Due to missing substituents at the p5rrazolyl carbon C5 and a hence likely ortho metallation, isomers 21a and 21b are not suited for his reaction (72). 

Indazole sind schwache Basen und konnen z.B. Natrium- oder Silber-Salze bilden. Die mittels UV-Spektroskopie bzw. Photoelektronenspektroskopie bestimmten pK-Werte liegen fur IH-indazol zwischen 1,01 und 1,31, fur 1-Methyl-1 H-indazol bei 0,42. 2-Methyl-2 H-indazol dagegen ist eine weitaus starkere Base, die pK-Werte wurden zwischen 1,72 und 2,02 gefun-den241 275 296,4 6 524 IH-lndazol besitzt auch schwach sauren Charakter (pK = 13,8688). 

H-Indazole formation is thought to proceed via a sequence of transition-metal-mediated N-amination by the terminal hydrazine nitrogen ( 15) and ring-closure by intramolecular hydroamination of the triple bond followed by tautomerization (15 16). 

A heterocyclization involving the N-2 atom of indazole affords [l,2,4]triazino[4,5-h]-indazoles (561) from the 3-carbohydrazinoindazole (78JHC1159,79JHC53). The corresponding pyrazolo[l,5-tf][l,2,4]triazine (562) has been prepared by the same procedure (8UHC1319). 

Dimethyl-1 H-indazol-3 -yl)-5 -pyridin-3 -yl-thiazol-4-yl] - [3 -(isopropyl-methyl-amino)-pyrrolidin-l-yl] -methanone 1 H Y-0 /-N xD vO... 

Chloro-7-methyl-1 H-indazol-3 -yl) -5 -pyridin-3 -yl-thiazole-4-carboxylic acid [3-(5-oxo-4,5-dihydro-lH-pyrazol-4-yl)-propyl]-amide aOJ tQTn o Y-O HN 7 H N... 

H-indazol/Pd — C), 815 (3-Diazo-3H-indazol/TiCl3) Malonsaure (2-Butinyl)- -dinitril E19b, 1205 (Carben-C,H-Insertion)... 

BENZYL-3-y-DIMETHYLAMINOPROPOXY-I H-INDAZOLE HYDROCHLORIDE see BBW500 BENZYL l-(2-(DIMETHYLAMINO)PROPYL)PYRROL-... 

V-Unsubstituted indazoles (R = H) behave like a mixture of N(1)H and N(2)H tautomers giving rise to o-aminobenzonitriles (190) similar to 1-substituted isomers and to benzimidazoles (191) like the isoindazoles (67HCA2244, 74JA2010, 74JA2014). 

Recently, Picciola et al. (8IFESI037) prepared some 2/f-indazole derivatives containing a phenylalkanoic acid residue with potential antiinflammatory activity (693). M.G. 18755 (R = CHMeC02H, R = R = R = H) and its lysine salt, M.G. 18334, showed greater activity than ibuprofen, and the homologous butyric acid derivative M.G. 18860 showed good activity as a platelet aggregation inhibitor. 

C8H8N2 3-methyl-1 H-indazole 3176-62-3 68.25 1.0605 2 13463 C8H803 3-hydroxy-5-methylbenzoic acid 585-81-9 47.17 1.2172 2... 

In different sections of this chapter, pyrazoles and indazoles C-linked to a metal or a metalloid have been described or they will be described in the preparative sections, including lithio derivatives (Section 4.04.2.1.7), pyrazolylmagnesium reagents (Section 4.04.2.3.7(iii)), chloromercury derivatives (Section 4.04.2.1.4(vii)) and silylpyrazoles (Section 4.04.3.1.2(H)). All these compounds are useful intermediates and some of their most characteristic reactions will be discussed here. 

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