反应详情

温度

110 °C

A mixture of 8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene, also named as 9-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 95 (300 mg, 0.80 mmol), 1-methyl-4-pyrrolidin-2-ylpiperidine (338 mg, 2.00 mmol), NaOtBu (232 mg, 2.40 mmol) and Pd(PtBu3)2 (20 mg, 0.04 mmol) in toluene (6 mL) was heated at 110° C. for 3 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (C18, gradient 10-65% MeOH in H2O) then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was freeze-dried from MeCN/H2O to afford 141 (20 mg, 16%) as a white solid. LCMS: RT 2.91 min [M+H]+ 462.4. 1H NMR (DMSO, 400 MHz): δ 8.18 (1H, d, J=8.95 Hz), 7.87 (1H, s), 7.77 (1H, s), 6.49 (1H, dd, J=9.03, 2.41 Hz), 6.13 (1H, d, J=2.36 Hz), 5.94-5.93 (1H, m), 4.45-4.40 (4H, m), 3.74 (1H, s), 3.45-3.43 (1H, m), 3.14-3.11 (1H, m), 2.78 (2H, s), 2.12 (3H, s), 1.99-1.72 (5H, m), 1.71-1.51 (3H, m), 1.47 (6H, dd, J=6.60, 1.90 Hz), 1.33-1.31 (3H, m)

1. washwas washed with MeOH
2. washthe product eluted with 2M NH3/MeOH
3. customThe resulting residue was purified by column chromatography (C18, gradient 10-65% MeOH in H2O)
4. washwas washed with MeOH
5. washthe product eluted with 2M NH3/MeOH
6. dry with materialThe resulting residue was freeze-dried from MeCN/H2O