反应详情

温度

50 °C

General procedure AA: To a mixture of 4-[4-(7-hydroxy-6-nitrofuro[3,2-c]pyridine-3-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (20.0 mg, 0.047 mmol), 1-(2,6-dichlorophenyl)propan-1-ol (28.6 mg, 0.14 mmol), triphenylphosphine (24.4 mg, 0.093 mmol) and THF (2 mL) at rt was added diisopropyl azodicarboxylate (37.7 mg, 0.186 mmol) dropwise, and the solution was flushed with nitrogen and heated to 50° C. for 4 h. The solvents were removed in vacuo, and the material was redissolved in EtOH (3 mL). Iron powder (30 mg, 0.5 mmol) and 5 drops of conc. HCl were added, and the solution was refluxed for 30 min. The solution was directly passed through a SCX cartridge, washed with MeOH and ejected with 2M NH3 in MeOH. The crude product was concentrated in vacuo, redissolved MeOH (1 mL) and purified via HPLC. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.06 (t, J=7.5 Hz, 3H), 1.93-2.05 (m, 2H), 2.09-2.17 (m, 2H), 2.33 (dt, J=13.7, 7.5 Hz, 1H), 2.48 (dd, J=14.3, 6.9 Hz, 1H), 2.78 (td, J=12.7, 2.7 Hz, 2H), 3.16-3.24 (m, 2H), 4.35 (tt, J=11.7, 4.1 Hz, 1H), 6.43 (t, J=7.5 Hz, 1H), 7.20-7.26 (m, 1H), 7.36 (d, J=8.1 Hz, 2H), 7.80 (s, 1H), 7.83 (s, 1H), 8.09 (s, 1H), 8.13 (s, 1H). MS (ES+): m/z 498.06/500.05 (100/72) [MH+]. HPLC: tR=2.65 min (ZQ3, polar—5 min).

1. customthe solution was flushed with nitrogen
2. customThe solvents were removed in vacuo
3. dissolutionthe material was redissolved in EtOH (3 mL)
4. temperaturethe solution was refluxed for 30 min
5. washwashed with MeOH
6. concentrationThe crude product was concentrated in vacuo
7. dissolutionredissolved MeOH (1 mL)
8. custompurified via HPLC
9. additionThe fractions containing the pure product
10. concentrationwere concentrated in vacuo