反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
实验步骤: 3-(2-Fluoro-4-methylsulfanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (0.13 g, 0.38 mmol) was dissolved in IMS (5 ml) before 1M NaOH (0.45 ml, 0.45 mmol) was added and the mixture heated at 60° C. for 2 hours. The reaction mixture was concentrated in vacuo and the residue was re-dissolved in THF (3 ml). 2-Aminooxy-2-methyl-propan-1-ol (100 mg, 0.56 mmol), DIPEA (0.20 ml, 1.1 mmol) and HATU (210 mg, 0.56 mmol) were added and the mixture stirred at room temperature. On completion of the reaction, the solvent was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic extract was washed with water, dried (MgSO4), and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si-PPC, DCM:MeOH, gradient 99:1 to 90:10) to give an orange solid. The orange solid was then purified by reversed phase HPLC (Phenomenex Luna 5 phenyl/hexyl 0.1% HCO2H in water on a gradient of acetonitrile) to provide the title compound (semiformate) as a yellow solid (7 mg, 5%). LCMS (method A): RT=5.87 min, M+H+=405. 1H NMR (d6-DMSO, 400 MHz) 1.10 (6H, s), 2.42 (3H, s), 3.20 (2H, s), 6.58 (1H, t, J=8.58 Hz), 6.91 (1H, dd, J=8.42, 2.06 Hz), 7.20 (1H, dd, J=12.05, 2.11 Hz), 7.37 (1H, dd, J=5.84, 1.11 Hz), 7.81 (1H, s), 8.23 (1H, d, J=5.83 Hz), 8.52 (1H, d, J=1.07 Hz).
was added
The reaction mixture was concentrated in vacuo
the residue was re-dissolved in THF (3 ml)
On completion of the reaction
the solvent was removed in vacuo
the residue was partitioned between ethyl acetate and water
The organic extract
was washed with water
dried (MgSO4)
concentrated in vacuo
The resultant residue was purified by flash chromatography (Si-PPC, DCM:MeOH, gradient 99:1 to 90:10)
to give an orange solid
The orange solid was then purified by reversed phase HPLC (Phenomenex Luna 5 phenyl/hexyl 0.1% HCO2H in water on a gradient of acetonitrile)
来源 ID: ord-39ac37a7175b4ab783115e7c3dc304d1