反应详情

温度

0 °C

A solution of 9-fluoro-10-(3-(5-formylisoxazol-3-yl)-3-hydroxybut-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide (90 mg, 0.22 mmol, 1.00 equiv), hydroxylamine hydrochloride (15 mg, 0.22 mmol, 1.00 equiv) in N,N-dimethylformamide (3 mL) was heated at 140° C. for 1 h. To this was added triethylamine (90 mg, 0.89 mmol, 4.00 equiv) at 0° C. To the mixture was added TEAA (70 mg, 1.50 equiv) dropwise with stirring at 0° C. The resulting solution was stirred for 12 h at 120° C. The reaction solution was diluted with DCM and washed with water. The crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005(Waters)): Column, XBridge Shield RP18 OBD Column, 5 um, 19*150 mm; mobile phase, Water with 10 mmolNH4HCO3 and CH3CN (15% CH3CN up to 70% in 10 min, up to 95% in 1 min, hold 95% in 1 min, down to 15% in 2 min); Detector, UV 254/220 nm. This gave the titled compound (5.4 mg, 6%).

1. stirringThe resulting solution was stirred for 12 h at 120° C
2. washwashed with water
3. customThe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005(Waters))
4. waitup to 95% in 1 min
5. customin 1 min
6. waitdown to 15% in 2 min)