methyl 1H-indazole-3-carboxylate → HCID 10680335, compound

To a solution of indazole-3-carboxylic acid methyl ester (40.7 g, 231 mmol) in anhydrous tetrahydrofuran (700 mL) cooled in an ice bath was added slowly solid potassium tert-butoxide (28.3 g, 252 mmol). The mixture was stirred at the same temperature for 1 hr prior to the addition of 2-iododopropane (34.4 mL, 367 mmol). The final mixture was stirred for 12 h at ambient temperature, and refluxed for 12 h. After cooling to room temperature, the mixture was filtered, and the collected solid was rinsed with tetrahydrofuran (100 mL). The filtrates were combined, and concentrated to dryness under reduced pressure, affording crude 1-isopropyl-1H-indazole-3-carboxylic acid methyl ester (49.7 g) as a pale yellow oil. The crude material was purified by flash silica gel chromatography eluting with hexane/ethyl acetate (9/1 to 3/1) to yield 1-isopropyl-1H-indazole-3-carboxylic acid methyl ester (43 g, 197 mmol, >99% pure). 1H-NMR (CD3OD, 300 MHz): δ (ppm) 8.1-8.0 (1H, d), 7.6 (1H, d), 7.4 (1H, t), 7.2 (1H, t), 5.0 (1H, quin), 3.9 (s, 3H), 1.5 (6H, d).

1. additionto the addition of 2-iododopropane (34.4 mL, 367 mmol)
2. temperaturerefluxed for 12 h
3. filtrationthe mixture was filtered
4. washthe collected solid was rinsed with tetrahydrofuran (100 mL)
5. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-f4f250c3a4bc4d56a757012c76afc3e5

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08044045B2