Hydrochloric Acid → HCID 57812517, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 4-(7-hydroxy-6-nitrofuro[3,2-c]pyridin-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (Intermediate 14) (20.0 mg, 0.0553 mmol), 1-(2,6-dichloro-3-fluorophenyl)ethanol (34.7 mg, 0.166 mmol), and PPh3 (43.6 mg, 0.166 mmol) in THF (1.0 mL, 12 mmol) under nitrogen was added dropwise diisopropyl azodicarboxylate (22.4 mg, 0.111 mmol), and the mixture was heated at 40° C. overnight. THF was evaporated, and iron powder (30.9 mg, 0.553 mmol), ethanol (1.5 mL, 26 mmol) and 1 drop of aq. 12 M HCl were added. The mixture was stirred at 70° C. for 20 minutes. Iron was taken out by stirring bar. 5 drops of aq. 12 M HCl were added, and the mixture was stirred at 70° C. for 2 h, passed through SCX-2 SPE cartridge and eluted by 2 M NH3 in methanol. This material was completely dried in vacuo overnight. Trimethylsilyl isocyanate (11.2 μL, 0.0830 mmol), DMF (1.0 mL, 13 mmol) and DIPEA (19.3 μL, 0.111 mmol) were added, and the mixture was stirred at room temperature for 1 h. The reaction mixture was filtered and purified using the MDPS to give the title compound. MS (ES+): m/z 465.16/467.18 [MH+]. HPLC: tR=0.72 min (HPLC-ACQUITY, Analytical). 1H NMR (400 MHz, CD3OD): δ=1.88 (d, J=6.8 Hz, 3H), 2.45-2.56 (m, 2H), 3.64 (t, J=5.8 Hz, 2H), 4.10 (d, J=2.5 Hz, 2H), 6.26 (br. s., 1H), 6.50 (q, J=6.8 Hz, 1H), 7.22 (t, J=8.7 Hz, 1H), 7.40 (dd, J=9.0, 4.9 Hz, 1H), 7.66 (s, 1H), 8.19 (br. s., 1H).

Provenance & Evidence