Synthesis
General procedure for the synthesis of methyl 1H-indazole-7-carboxylate from methyl 2-amino-3-methylbenzoate: To a solution of methyl 2-amino-3-methylbenzoate (17.5 g, 106 mmol) in chloroform (300 mL) was slowly added acetic anhydride (22.6 mL, 239 mmol, 2.3 eq.), and the temperature of the reaction was controlled to be lower than 40°C. The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was stirred at room temperature for 1 hour and then potassium acetate (3.00 g, 30.6 mmol, 0.3 eq.) and isoamyl nitrite (30.6 mL, 228 mmol, 2.2 eq.) were added sequentially. The reaction mixture was heated to reflux for 24 hours and subsequently cooled to room temperature. The reaction mixture was washed with saturated aqueous sodium bicarbonate, the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Methanol (100 mL) and 6N hydrochloric acid (100 mL) were added to the residue and the mixture was stirred at room temperature for 18 hours. The volatiles were removed under reduced pressure and the residue was ground with ethyl acetate (100 mL). The solid product was separated by filtration, washed with ethyl acetate (20 mL) and dried to give 15.3 g (68% yield) of methyl 1H-indazole-7-carboxylate hydrochloride. Product characterization data: 1H NMR (500 MHz, DMSO-d6) δ; 13.3 (broad peak, 1H), 8.26 (double peak, 1H), 8.12 (double peak, 1H), 8.25 (double-double peak, 1H), 7.27 (triple peak, 1H), 3.97 (single peak, 3H); MS (APCI) m/z 177 (M++1).
References
[1] Patent: WO2004/29050, 2004, A1. Location in patent: Page 64
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 14, p. 3933 - 3937
[3] Journal of Organic Chemistry, 2016, vol. 81, # 15, p. 6855 - 6861
[4] Patent: WO2007/121578, 2007, A1. Location in patent: Page/Page column 29
[5] Patent: WO2008/65508, 2008, A1
