反应详情

温度

90 °C

tert-Butyl[2-{[(6-chloropyridin-3-yl)carbonyl]amino}-4-(2-thienyl)phenyl]carbamate F (20 mg, 0.088 mmol) was dissolved in 1 mL of DMSO and treated with Et3N (0.010 mL) and tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate (20 mg, 0.047 mmol). The mixture was stirred at 90° C. for 18 h, partitioned between EtOAc and saturated NaHCO3, dried (MgSO4), filtered and concentrated), concentrated and the residue was purified by chromatography on SiO2 (EtOAc/CH2Cl2, 0% to 100%). The residue was dissolved in 1 mL of 1:1 TFA/CH2Cl2, stirred for 1 h and concentrated. Neutralization with EtOAc/sat'd NaHCO3 extraction and drying (MgSO4) gave desired product, N-[2-amino-5-(2-thienyl)phenyl]-6-(2,7-diazaspiro[3.5]non-7-yl)nicotinamide, which was confirmed by MS (ESI+): cal'd [M+H]+ 420.2, obs'd 420.1.

1. custompartitioned between EtOAc and saturated NaHCO3
2. dry with materialdried (MgSO4)
3. filtrationfiltered
4. concentrationconcentrated),
5. concentrationconcentrated
6. customthe residue was purified by chromatography on SiO2 (EtOAc/CH2Cl2, 0% to 100%)
7. dissolutionThe residue was dissolved in 1 mL of 1:1 TFA/CH2Cl2
8. stirringstirred for 1 h
9. concentrationconcentrated
10. extractionNeutralization with EtOAc/sat'd NaHCO3 extraction
11. dry with materialdrying (MgSO4)