反应详情

To a mixture of Na2CO3 (53 mg, 0.50 mmol) and Pd(OAc)2 (3 mg, 0.013 mmol) in NMP (0.5 mL) was added i-PrOH (3 drops) and water (2 drops). The mixture was stirred at RT for 5 min. A solution of (R)-tert-butyl 1-(4-(2-bromo-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate (18, 246 mg, 0.496 mmol) in NMP (1.0 mL) was added. The mixture was heated to 140° C. and then K4[Fe(CN)6].3H2O (209 mg, 0.496 mmol) was added. The mixture was heated at 140° C. for 12 h. After cooling to RT, the mixture was diluted with water (10 mL), and extracted with EtOAc (20 mL×2). The combined extracts were washed with brine, dried over MgSO4, and concentrated to give crude product. This was purified by column chromatography on silica gel, and eluted with 20-35% EtOAc in petroleum ether to provide (R)-tert-butyl 1-(4-(2-cyano-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate (20). MS: m/z, 418 (20%), 443 (100%, M+1), 465 (95%, M+23).

1. temperatureThe mixture was heated to 140° C.
2. addition3H2O (209 mg, 0.496 mmol) was added
3. temperatureThe mixture was heated at 140° C. for 12 h
4. temperatureAfter cooling to RT
5. extractionextracted with EtOAc (20 mL×2)
6. washThe combined extracts were washed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated
9. customto give crude product
10. customThis was purified by column chromatography on silica gel
11. washeluted with 20-35% EtOAc in petroleum ether