* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With N-Bromosuccinimide In dichloromethane at 20℃; for 1 h;
To a solution of 5-chloro- 1H-indazole (2.5 g, 16.1 mmol) in dichloromethane (150 mL) was added N-bromosuccinimide (2.9 g, 16.6 mmol) and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (100 mL), washed with water (50 mL) and brine (50 mL), dried over sodium sulfate and concentrated under reduced pressure to afford 3-bromo-5-chloro-1H-indazole (3.7 g, 94percent) as a brown solid. ‘H NMR (DMSO-d6, 400 MHz) 13.63 (s, 1H), 7.67 — 7.59 (m, 2H), 7.49 — 7.44 (m, 1H). TLC: 50percent ethyl acetate/heptane (R1: 0.43).
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 3h;
General procedure: 3-Iodoindazoles were obtained by direct iodination of commercial indazoles by the method previously described by Bocchi [28] with slight modifications. A solution of 1H-indazole (3 g, 25.4 mmol), iodine (12.7 g, 50.03 mmol) and potassium hydroxide (5.34 g, 95.25 mmol)in DMF (7 mL) was stirred for 3 h at room temperature. The reaction was quenched by dilution with saturated solution of sodium bisulfite (150 mL) and a precipitated was formed. The precipitated was filtered over vacuum and washed with water (3 × 30 mL). The solid was left to dry at 30 C in a vacuum oven overnight obtaining 6.17 g of a pale yellow solid. Yield: 100%; m.p.: 136-138 C (lit.:[36] 134-136 C); IR (KBr) nu (cm-1): 3086 (NH); 424 (C-I). 1H-NMR delta (ppm): 13.50 (1H, s, H-1); 7.55(1H, d, J = 8.6 Hz, H-7); 7.45-7.40 (2H, m, H-6 and H-4); 7.19 (1H, dd, J = 7.5 Hz, H-5). 13C-NMR delta(ppm): 140.41; 127.22; 126.79; 121.23; 120.39; 110.51; 93.49; HRMS calculated for C7H5IN2: 243.9497,Found: 243.9499.3-Iodo-1H-indazole (1a). 3-Iodoindazoles were obtained by direct iodination of commercial indazoles by the method previously described by Bocchi [28] with slight modifications. A solution of 1H-indazole(3 g, 25.4 mmol), iodine (12.7 g, 50.03 mmol) and potassium hydroxide (5.34 g, 95.25 mmol) in DMF(7 mL) was stirred for 3 h at room temperature. The reaction was quenched by dilution with saturated solution of sodium bisulfite (150 mL) and a precipitated was formed. The precipitated was filtered over vacuum and washed with water (3 30 mL). The solid was left to dry at 30 C in a vacuum oven overnight obtaining 6.17 g of a pale yellow solid. Yield: 100%; m.p.: 136-138 C (lit.: [36] 134-136 C)
85.3%
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃;
To a mixture of 5-chloro-1H-indazole(2.0 g, 13.1 mmol, 1.0 eq.), KOH (2.4 g,45.8 mmol) in DMF was added ?2 (6.6 g, 26.1 mmol, 2.0 eq.). The mixture was stirred at rt overnight, then quenched by aqueous Na2S2O4 solution. The mixture was extracted with EtOAc (2 x 50 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography (PE/EA =10:1) to provide 5-chloro-3 -iodo- 1H-indazole (3.1 g, 85.3%).
85.3%
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃;
To a mixture of 5-chloro-lH-indazole (2.0 g, 13.1 mmol, 1.0 eq.), KOH (2.4 g, 45.8 mmol) in DMF was added I2 (6.6 g, 26.1 mmol, 2.0 eq.). The mixture was stirred at r.t. overnight, then quenched by aqueous Na2S204 solution. The mixture was extracted with EtOAc (2 x 50 mL). The combined organic layers were dried over anhydrous Na2S04 and concentrated. The residue was purified by column chromatography (PE/EA =10: 1) to provide 5-chloro-3-iodo-lH-indazole (3.1 g, 85.3%).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
