反应详情

To a stirred solution of 4-chloro-7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazine (I-2A-1b; 2.00 g, 5.13 mmol) in DME (30 ml) at 23° C. was added diisopropylethylamine (0.940 ml, 5.36 mmol) over 5 minutes. In a separate flask, a solution of 3-ethylaminoazetidine-3-carboxylic acid amide hydrochloride salt (I-2A-1h; 1.16 g, 5.37 mmol) in water (10 ml) was treated with diisopropylethylamine (1.90 ml, 10.8 mmol) over 5 minutes. The aqueous solution was then added to the DME solution over a 10-minute period while maintaining the reaction temperature below 28° C. After 2 hours, water (20 ml) was added over 5 minutes, and an orange solid precipitated from the reaction. The solid product was collected by filtration, washed with additional water, and then air dried by pulling low house vacuum across the sample to afford 2A-1 (2.15 g, 84%) as an off-white solid: +ESI MS (M+1) 496.4; 1H NMR (400 MHz, CD3OD) δ 7.46-7.35 (m, 4H), 7.31 (d, J=7.7 Hz, 2H), 7.21 (d, J=7.7 Hz, 2H), 5.14 (br d, J=8.3 Hz, 1H), 4.77 (br d, J=8.3 Hz, 1H), 4.61 (br d, J=8.3 Hz, 1H), 4.22 (br d, J=8.3 Hz, 1H), 2.54 (q, J=7.1 Hz, 2H), 2.45 (s, 3H), 1.14 (t, J=7.1 Hz, 3H).

1. temperaturewhile maintaining the reaction temperature below 28° C
2. customan orange solid precipitated from the reaction
3. filtrationThe solid product was collected by filtration
4. washwashed with additional water
5. customair dried
6. customto afford 2A-1 (2.15 g, 84%) as an off-white solid