反应详情

To a solution of tert-butyl 4-((2-amino-1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (64 mg, 0.099 mmol) in dimethylformamide (0.7 mL) at 0° C. was added cyanuric chloride (18.2 mg, 0.10 mmol). The ice bath was removed and stirring continued for 5 h. The reaction was diluted with diethyl ether and quenched by addition of water. After stirring for 10 min, the ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (18%→25% ethyl acetate/n-hexane) gave 31 mg (50%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ0 8.08 (s, 1H), 7.68 (d, J=1.2 Hz, 1H), 7.29 (dd, J=8.6, 5.2 Hz, 2H), 7.24 (s, 1H), 7.00 (dd, J=8.9, 8.5 Hz, 2H), 5.71 (s, 1H), 5.69 (d, J=10.7 Hz, 1H), 5.64 (d, J=10.7 Hz, 1H), 3.76 (m, 3H), 3.61 (t, J=8.2 Hz, 2H), 3.58 (d, J=8.9 Hz, 1H), 3.03 (m, 2H), 2.14 (m, 2H), 1.90 (m, 2H), 1.43 (s, 9H), 0.92 (m, 2H), −0.03 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.5 (d, J=246 Hz), 155.0, 144.3, 137.6, 128.9 (d, J=8.6 Hz), 127.6, 125.9, 124.4, 122.92, 122.87, 121.0, 116.6, 115.4(d, J=21 Hz), 82.1, 79.6, 78.6, 68.0, 66.5, 41.2, 40.0 (br), 32.0, 28.5, 17.9, −1.3. Mass spec.: 629.35 (MH)+

1. customThe ice bath was removed
2. additionThe reaction was diluted with diethyl ether
3. customquenched by addition of water
4. stirringAfter stirring for 10 min
5. washthe ethereal was washed with water (2×)
6. dry with materialbrine, dried over magnesium sulfate
7. concentrationconcentrated
8. customColumn chromatography (18%→25% ethyl acetate/n-hexane) gave 31 mg (50%) as a colorless oil