Indazole, 3-chloro

Benzyl-S-oxy-indazole Chloro acetonitrile Hydrogen Chloride... 

All the 3-diazoindazoles 2, irradiated in an aromatic solvent (benzene, p-chlorotoluene, benzonitrile, 1,2-dimethoxybenzene), gave by ring substitution the corresponding 3-arylindazoles in variable yields (66LA17). 3-Diazoindazole 2b, irradiated in pyridine and in thiophene, gave the 6-chloro-3-(2-pyridyl)-indazole and the 6-chloro-3-(2- or 3-thiophenyl)-indazole (66LA17). 

The synthesis of pazopanib (1) involves sequential animation of 2,4-dichloropyrimidine 25 with 6-amino-2,3-dimethylindazole 24 and 5-amino-2-methyl-benzenesulfonamide 28. The 6-amino-2,3-dimethylindazole 24, on the other hand, was prepared from 2-ethylphenylamine 20 via 5-nitration with fuming nitric acid and concentrated sulfuric acid, followed by treatment with isoamyl nitrite and acetic acid to produce 6-nitro-3-methylindazole 22. The 6-nitro group was reduced with stannous chloride and concentrated HC1 in glyme and subsequently methylated at the C2 position of the indazole ring with trimethyloxonium tetrafluoroborate in acetone to produce 6-amino-2,3-dimethylindazole 24. The resultant indazole 24 was condensed with 2,4-dichloropyrimidine 25 in the presence of sodium bicarbonate in ethanol/THF and subsequent iV-methylation with iodomethane and cesium carbonate to produce 27. The 2-chloro group of pyrimidine was then allowed to react with 5-amino-2-methyl-benzenesulfonamide 28 in catalytic HCl/isopropanol and heated to reflux to deliver pazopanib hydrochloride (1) in good yield. 

Thermal cyclization was also the route employed to prepare 9-hydroxy-7-methyl-l/f-pyrazolo[3,4-/]quinoline (74) from the 6-aminoindazole/ethyl acetoacetate condensation adduct shown in Equation (41) <92JMC4595>. The hydroxyl substituent of compound (74) was then converted (POCl3, DMF) to a chloro, which in turn was displaced by treatment with aryl amines to give tricyclics with potent in vivo immunostimulatory activity like that noted for regioisomeric l//-imidazo[4,5-/]quinolines but unlike the inactive pyrazolo[4,3-/]quinolines. Although it was noted with some interest that none of the linear tricyclic isomer had been isolated, this finding actually parallels that reported earlier for the similar condensation of 1- and (V(6)-alkyl and unsubstituted 6-amino-indazoles with diethyl ethoxymethylenemalonate <83JHC1351>. 

NMR spectra of vicarious /V-alkylation products of 7-nitroinduzoles [672], l-benzylamino-3-nitroindazole [673], 1- and 6-nitroglucosylindazoles [674], l-acetyl-3-chloro-6-nitroindazole [675], the products of methylation and acetylation of 5- and 6-nitroindazoles in various solvents (CDC13, DMSO, acetone) [676], 5-nitro-7-methylindazole [677], 2-substituted 4,6-dinitroindazole [678], several dinitro indazoles [679], 6-nitroindazole derivatives [680], 44 nitrated 1- and 2-methylindazoles having H, Cl, and Br substituents in position 3 [681] have been obtained. II NMR data of some nitroindazoles are presented in a few studies [682-684],... 

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... 

Chloro-7-methyl-lH-indazol-3-yl)-5-pyridin-3-yl- thiazol-4-yl]-(2,3,5,6-tetrahydro-[l,2 ]bipyrazinyl-4-yl)- methanone Clvk-N, r N o n- n Y... 

Chloro-2-methyl-4-phenylquinazoline 1-oxide gives l-acetyl-5-chloro-3-phenyl-l//-indazole on irradiation. This transformation is believed to proceed by rearrangement of the oxaziridines formed as primary isomerization products. ... 

The reverse of the above transformation, i.e., conversion of a quinazoline into an indazole, has been observed. Thus photolysis of 6-chloro-2-methyl-4-phenylquinazoline 1-oxide provided l-acetyl-5-chloro-3-phenylindazole, and most probably proceeded via 7-chloro-2-methyl-5-phenyl-3,l,4-benzo-oxadiazepine because the latter yields the same indazole on photolysis. ... 

Polyhalogenoalkanes and dihalogenoethanes have been extensively used to prepare, under PTC conditions, poly(pyrazol-l-yl)alkanes (number of pyrazoles = 2,3,4) and l,2-di(pyrazol-l-yl)ethanes <840PP299,86H(24)2233>. The reaction of pyrazoles with 1,2-dibromoethane in PTC conditions affords a mixture of 7V-ethenylpyrazoles and 1,2-bispyrazolylethanes <88JHC77i> it is also possible to carry out the reaction in two steps through l-chloro-2-(pyrazol-l-yl)ethane. Indazole affords a mixture of l,2-bis(indazol-l-yl)ethane and l-(indazol-l-yl)-2-(indazol-2-yl)ethane. 

Some modifications of amino and hydrazino groups were also performed. An amino group can be replaced in the reaction with amines, although in low yield.442 To the few known pyridazinonimines some new compounds have been added. The imines (203) are prepared from the corresponding pyridazinium salts and sodium hydride.443 Hydrazinopyridazines upon nitrosation are transformed into azido- or tetrazolopyridazines. The reaction can be complicated by aza-transfer reactions with a heterocyclic diazo compound. For example, 3-chloro-6-hydrazinopyridazine, when treated with 3-diazoindazole in methanol, is transformed into a mixture of 3-amino-6-chloropyridazine, 6-chloro-, and 6-methoxytetrazolopyridazine, indazole and its 3-amino and 3-azido derivatives.444... 

Indazoles.—iV-Aryl-o-azidobenzamides (391) yield the chloro-indazoles (392) on treatment with thionyl chloride.The formation of 1,3-diphenylindazole (393) by the action of trifluoromethanesulphonic anhydride on benzaldehyde... 

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