Triethylamine → HCID 58052448, compound

Participants

Reaction Conditions

Reaction Steps

6-(N-acetylacetamido)-3,5-diiodopyridin-2-yl acetate (600 mg, 1.23 mmol) was dissolved in THF (40 mL) and copper(I) iodide (7.02 mg, 0.037 mmol) and bis(triphenylphosphine)palladium(II) chloride (25.9 mg, 0.037 mmol) were added. The mixture was bubbled under N2 at 0° C. for 5 min. Triethylamine (0.514 ml, 3.69 mmol) was added and the mixture was bubbled with N2 at 0° C. for 3 min. 1-ethynyl-4-methylbenzene (143 mg, 1.229 mmol) in THF (2 ml) was added and the mixture was stirred at 0° C. for 4 hr. Then mixture was warmed up to 23° C. and stirred for 16 hrs., then cooled to 0° C. Sodium acetate (403 mg, 4.92 mmol) and copper(II) chloride (496 mg, 3.69 mmol) were added, and 30 mL of methanol was added. The flask was purged with CO from a balloon and stirred at 23° C. overnight. The volatiles were removed under vacuum. 40 mL of 1.0N HCl and 100 mL of CH2Cl2 were added. The mixture was stirred at 23° C. for 30 min. The mixture was filtered and solid washed with 60 mL of CH2Cl2. The filtrates were combined and separated. The organic layer was dried over sodium sulfate, filtered and concentrated. The 440 mg of solid crude mixture including methyl 6-(N-acetylacetamido)-5-iodo-2-p-tolylfuro[2,3-b]pyridine-3-carboxylate and methyl 6-acetamido-5-iodo-2-p-tolylfuro[2,3-b]pyridine-3-carboxylate was dissolved in MeOH and stirred with SODIUM HYDROXIDE (8 ml, 8.00 mmol) at 60° C. for 2 hrs. The MeOH was removed under vacuum and 30 ml water was added. The aqueous was extracted with ethyl ether to remove neutral impurities. The aqueous layer was acidified to pH 4-5 and precipitate was filtered and washed w/water and dried under vacuum to afford 300 mg (0.76 mmol, 62%) 6-amino-5-iodo-2-p-tolylfuro[2,3-b]pyridine-3-carboxylic acid. MS-ES [M+H]+=395.0; LC-RT=1.14 min, Method A

Provenance & Evidence