反应详情

To a solution of 2-((1-(tert-butoxycarbonyl)-4-(4-fluorophenyl)piperidin-4-yl)methoxy)-2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetic acid (100 mg, 0.154 mmol) and ammonia (7 M in methanol, 0.110 mL, 0.771 mmol) in dimethylformamide (2 mL) at 0° C. was added PyBOP (96 mg, 0.19 mmol). The ice bath was removed and stirring continued for 1 h. The reaction was quenched by addition of water and diluted with diethyl ether. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (50%→85% ethyl acetate/n-hexane) gave 89 mg (89%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.02 (s, 1H), 7.57 (d, J=1.8 Hz, 1H), 7.27 (dd, J=8.9, 5.2 Hz, 2H), 7.00 (dd, J=8.6, 8.5 Hz, 2H), 6.95 (d, J=1.5 Hz, 1H), 6.48 (d, J=2.7 Hz, 1H), 6.05 (d, J=2.4 Hz, 1H), 5.65 (s, 2H), 5.23 (s, 1H), 3.66 (m, 2H), 3.60 (t, J=8.1 Hz, 2H), 3.51 (d, J=8.9 Hz, 1H), 3.41 (d, J=8.9 Hz, 1H), 3.01 (m, 2H), 2.10 (m, 2H), 1.80 (m, 2H), 1.40 (s, 9H), 0.91 (m, 2H), −0.05 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 172.5, 161.5 (d, J=246 Hz), 155.0, 146.1, 138.42, 138.39, 128.7 (d, J=7.7 Hz), 128.5, 127.8, 125.5, 122.9, 122.6, 119.7, 115.4 (d, J=21 Hz), 82.1, 79.5, 78.3, 67.8, 41.2, 40.0 (br), 32.2, 32.1, 28.5, 17.9, −1.3. Mass spec.: 647.35 (MH)+.

1. customThe ice bath was removed
2. customThe reaction was quenched by addition of water
3. additiondiluted with diethyl ether
4. washThe ethereal was washed with water (2×)
5. dry with materialbrine, dried over magnesium sulfate
6. concentrationconcentrated
7. customColumn chromatography (50%→85% ethyl acetate/n-hexane) gave 89 mg (89%) as a foam solid