反应详情

温度

0 °C

Methyl iodide (1.021 mL, 16.40 mmol) was added dropwise to a stirred suspension of N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine (4 g, 10.93 mmol, Example 3 starting material) and potassium carbonate (2.267 g, 16.40 mmol) in DMF (40 mL) at 0° C. under nitrogen. The resulting suspension was stirred at 0° C. for 15 minutes and was allowed to warm to room temperature. The reaction mixture was stirred at room temperature overnight, filtered off and washed with ethyl acetate. The filtrate was concentrated to dryness, diluted with dichloromethane (40 ml), washed with water (40 ml), brine (40 ml), dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography on silica gel eluting with 0 to 45% ethyl acetate in petroleum ether to afford N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-N-methyl-1H-indazol-4-amine (3.4 g, 82%) as a pale orange solid. NMR Spectrum: (DMSOd6) 3.50 (s, 3H), 3.71 (s, 3H), 5.63 (s, 2H), 6.19 (d, 1H), 6.89 (d, 2H), 7.16 (d, 1H), 7.29 (d, 2H), 7.49 (dd, 1H), 7.81 (d, 1H), 7.96 (d, 1H), 8.00 (s, 1H); Mass spectrum: MH+ 380.

1. temperatureto warm to room temperature
2. stirringThe reaction mixture was stirred at room temperature overnight
3. filtrationfiltered off
4. washwashed with ethyl acetate
5. concentrationThe filtrate was concentrated to dryness
6. additiondiluted with dichloromethane (40 ml)
7. washwashed with water (40 ml), brine (40 ml)
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography on silica gel eluting with 0 to 45% ethyl acetate in petroleum ether