反应详情

温度

55 °C

A mixture of 14A (120 mg, 0.34 mmol) and 1-(3-fluorobenzyl)-1H-indazole-5-amine (81.0 mg, 0.34 mmol; prepared as described in US 2003/0186983 A1) in CH3CN (1.2 ml) was heated at 55° C. for 45 min. After cooling to rt, tert-butyl piperidin-4-ylcarbamate (672 mg, 3.34 mmol) was added and the mixture was heated at 60° C. for 16 h. After cooling to rt. this mixture was then diluted with CH3CN (2.4 mL), and heated at 70° C. for 4 h and at 80° C. for 4 d. The reaction mixture was concentrated in vacuo and the residue was purified by prep HPLC to give 21A (52 mg, 27%). It has an analytical HPLC retention time=2.86 min (Chromolith SpeedROD column 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4 over 4 minutes, 4 mL/min, monitoring at 220 nm) and a LC/MS M++H=582+.

1. temperatureAfter cooling to rt
2. temperaturethe mixture was heated at 60° C. for 16 h
3. temperatureAfter cooling to rt
4. temperatureheated at 70° C. for 4 h and at 80° C. for 4 d
5. concentrationThe reaction mixture was concentrated in vacuo
6. customthe residue was purified by prep HPLC