Synthesis
The general procedure for the synthesis of 3-chloro-1H-indole-5-aniline using 3-chloro-5-nitro-1H-indazole as starting material was as follows: 1.00 g (5.06 mmol) of 3-chloro-5-nitro-1H-indazole was suspended in 50 mL of ethanol, followed by the addition of 5.71 g (25.3 mmol) of tin chloride dihydrate. The reaction mixture was stirred under reflux conditions overnight. Upon completion of the reaction, saturated aqueous sodium bicarbonate was added to the mixture to neutralize the reaction system, followed by three extractions with ethyl acetate. The organic phases were combined, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to remove the solvent. The resulting crude product was ground with 10% butyl methyl ether and the solid product was collected by filtration. A final 544 mg of the target compound was obtained with a purity of 90% and a yield of 58% of the theoretical value.
References
[1] Journal of Chemical Research, Miniprint, 1990, # 11, p. 2601 - 2615
[2] Journal of Medicinal Chemistry, 2003, vol. 46, # 26, p. 5663 - 5673
[3] Patent: US2016/52884, 2016, A1. Location in patent: Paragraph 0649-0652
[4] Patent: KR2015/137095, 2015, A. Location in patent: Paragraph 0867-0870
