Sodium Hydroxide → 3-(2-Fluoro-4-methylsulfanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-hydroxy-1,1-dimethyl-ethoxy)-amide

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence