Sodium Hydroxide → HCID 59596576, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydroxide (0.9 mL, 1M) was added to a suspension of 7-(2-fluoro-4-iodo-phenylamino)-5-methyl-5H-pyrrolo[3,2-c]pyridazine-6-carboxylic acid ethyl ester (242 mg, 0.55 mmol) in IMS (10 ml) and the reaction heated at 70° C. for 2 hours. The reaction mixture was concentrated in vacuo and the residue azeotroped with toluene (×3) to give a solid. The resultant crude solid was suspended in THF and HOBT (103 mg, 0.77 mmol), EDCI (136 mg, 0.69 mmol), DIPEA (0.144 ml, 0.83 mmol) and O-(2-vinyloxy-ethyl)-hydroxylamine (85 mg, 0.825 mmol) were then added and the reaction stirred at room temperature for 72 hours. The mixture was then concentrated in vacuo and the resultant residue dissolved in ethyl acetate (20 ml) and washed with water. The organic layer was separated, dried (Na2SO4), and filtered before concentrating in vacuo. The crude residue was purified by flash chromatography (Si-PPC, gradient 0-90% ethyl acetate in cyclohexane then 20% methanol in ethyl acetate) to yield the title compound as an orange solid (148 mg, 54%). LCMS (method B): RT=2.64 min, M+H+=498.

Provenance & Evidence