57% |
Stage #1: 5-bromo-6-methyl-1H-indazole With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.25h;
Stage #2: iodomethane In tetrahydrofuran; mineral oil for 1.5h; Cooling with ice; |
1.4
Step 45-bromo-1,6-dimethyl-1H-indazole (Compound A4)Compound (2.16 g, 10.2 mmol) was dissolved in THF (45 mL). To this, 60% sodium hydride (0.61 g, 15.3 mmol) was added, and the mixture was stirred at room temperature for 15 minutes. Under ice-cooling, methyl iodide (1.26 mL, 20.5 mmol) was added, and the mixture was stirred for 1.5 hours. After water was added to the reaction mixture, extraction with ethyl acetate, washing with brine, and then drying over anhydrous sodium sulfate were performed. The solvent was evaporated off under reduced pressure, and the residue was purified by flash column chromatography (hexane/ethyl acetate = 85/15 to 30/70) to give Compound A4 (1.31 g, yield: 57%) as a colorless crystal. ESI-MS m/z: 225 [M+H] +; 1H-NMR (CDCl3)δ(ppm): 2.55 (s, 3H), 4.03 (s, 3H), 7.26 (s, 1H), 7.86 (d, J = 0.9 Hz, 1H), 7.96 (d, J = 0.9 Hz, 1H). |
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Stage #1: 5-bromo-6-methyl-1H-indazole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.166667h; Inert atmosphere;
Stage #2: iodomethane In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; |
163.1
1 eq. of 5-bromo-6-methyl-1H-indazole was dissolved in DMF at 0 °C under N2. Then, 2.0 eq. of sodium hydride in DMF was added to the previous solution. The reaction mixture was stirred for 10 mins. In next step, 1.05 eq. of methyl iodide was added. The reaction was left to reach room temperature and stirred for 1 hours. The reaction was quenched by cooled saturated ammonium chloride solution. The desired product was extracted by EtOAc for 3 times. Next, the organic layer was washed by saturated NaCl solution and dried by anhydrous Na2SO4. The solvent was removed and the crude product was purified by liquid column chromatography with EtOAc/hexanes. |