反应详情

In a 25 mL sealable tube under nitrogen were combined 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylic acid (400 mg, 1.41 mmol) and 3-(aminomethyl)-4-ethyl-6-methyl-2(1H)-pyridinone.HCl (401 mg, 1.98 mmol) in DMSO (15 mL). 1-hydroxy-7-azabenzotriazole (308 mg, 2.26 mmol) was added and the resulting mixture was degassed with nitrogen for 10 minutes. N-methylmorpholine (0.64 ml, 5.79 mmol) and EDC (433 mg, 2.26 mmol) were added, the vessel was sealed, and the mixture was stirred at room temperature for 2 days. The mixture was poured onto 10 mL of ice-water and solids crashed out. 10% K2CO3 was added to adjust the pH˜8-9 and the contents were stirred for 10 min and then allowed to stand for another 10 min. Solids were filtered and air-dried. DMF along with some water were added and solids that precipitated were filtered. DCM was added and the contents purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in EtOAc along with some hexanes. Solids that precipitated were filtered and dried to afford the title compound as a white solid (504 mg, 82%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.63 (t, J=4.80 Hz, 1H) 8.37 (s, 1H) 8.20 (s, 1H) 7.70 (d, J=1.26 Hz, 1H) 5.93 (s, 1H) 5.06 (quin, J=6.57 Hz, 1H) 4.37 (s, 1H) 4.35 (s, 1H) 2.52-2.58 (m, 2H) 2.14 (s, 3H) 1.47 (s, 3H) 1.45 (s, 3H) 1.10 (t, J=7.58 Hz, 3H); LC-MS (ES) m/z=431.0/433.0

1. customIn a 25 mL sealable tube under nitrogen were combined
2. customthe resulting mixture was degassed with nitrogen for 10 minutes
3. customthe vessel was sealed
4. stirringthe contents were stirred for 10 min
5. waitto stand for another 10 min
6. filtrationSolids were filtered
7. customair-dried
8. additionDMF along with some water were added
9. customsolids that precipitated
10. filtrationwere filtered
11. additionDCM was added
12. customthe contents purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
13. customSolids that precipitated
14. filtrationwere filtered
15. customdried