ChemicalBook CAS DataBase List 7-METHYL (1H)INDAZOLE

7-METHYL (1H)INDAZOLE synthesis

12synthesis methods

Product Name:7-METHYL (1H)INDAZOLE
CAS Number:3176-66-7
Molecular formula:C8H8N2
Molecular Weight:132.16

87-62-7

3176-66-7

General procedure for the synthesis of 7-methyl-1H-indazole from 2,6-dimethylaniline: tert-butyl nitrite (52 mL) was slowly added to a solution of chloroform (750 mL) of 2,6-dimethylaniline (25 g, 206 mmol) at room temperature and protected by nitrogen, stirred for 20 min, then potassium acetate (40 g, 412 mmol) and 18-crown-6 ( 5.4 g, 20.6 mmol). The reaction mixture was heated to reflux for 3 hours, followed by cooling to room temperature and continued stirring for 15 hours. Upon completion of the reaction, the solids in the mixture were removed by vacuum filtration and the solids were washed with chloroform (400 mL). The filtrates were combined, washed with water (2 x 250 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by fast column chromatography on silica gel, using hexane/ethyl acetate (9:1) as eluent to afford 7-methyl-1H-indazole as an orange solid (23 g, 85% yield). The structure of the product was confirmed by 1H NMR (CDCl3): δ 2.60 (s, 3H), 7.10 (m, 2H), 7.70 (d, 1H), 8.10 (s, 1H).

87-62-7
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3176-66-7
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Yield: 85%

Reaction Conditions:

Stage #1:2,6-dimethylaniline with tert.-butylnitrite in chloroform at 20; for 0.333333 h;
Stage #2: with 18-crown-6 ether;potassium acetate in chloroform at 20; for 18 h;Heating / reflux;

Steps:

33.A
Example 33; 3-{2-Methyl-4-[1-(4-trifluoromethylphenyl)-1H-indazol-7- ylmethylsulfanyllphenvHpropionic Acid; Step A; 7-Methyl-lH-indazole; Add tert-butyl nitrite (52 mL) to a solution of commercially available 2,6- dimethylaniline (25 g, 206 mmol) in chloroform (750 mL) at room temperature under nitrogen, stir the mixture for 20 min and add potassium acetate (40 g, 412 mmol) and 18- crown-6 (5.4 g, 20.6 mmol). Heat the mixture at reflux for 3 h, cool to room temperature and stir for an additional 15 h. Remove the solids from the cooled mixture by vacuum filtration and wash with chloroform (400 mL). Wash the filtrate with water (2 x 250 mL), dry over MgS04 and remove the solvents were removed under reduced pressure. Purify the residue by flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (9: 1), to afford 7-methyl-lH-indazole as an orange solid (23 g, 85%): IH NMR (CDC13) 8 2.60 (s, 3H), 7.10 (m, 2H), 7.70 (d, 1H), 8. 10 (s, 1H).

References:

Location in patent:Page/Page column 108-109