Water → HCID 50996946, compound

Participants

Reaction Steps

A mixture of the compound of Reference Example 25 (50 mg, 0.10 mmol), 2-(4-aminopiperidin-1-yl)-2-oxoethanol hydrochloride (24 mg, 0.13 mmol), HOBt (21 mg, 0.16 mmol), WSCD (30 mg, 0.16 mmol) and triethylamine (21 mg, 0.21 mmol) in DMF (2 ml) was stirred at room temperature for 2 days. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate, and extracted twice with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by aminosilica gel column chromatography (eluate, ethyl acetate) to give 6-ethyl-3-[ethyl(trifluoroacetyl)amino]-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (40 mg, 65%) as a colorless amorphous solid. A mixture of the 6-ethyl-3-[ethyl(trifluoroacetyl)amino]-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (40 mg, 0.065 mmol) and potassium carbonate (18 mg, 0.13 mmol) in methanol (3 mL) was stirred at room temperature for 3 hr. Water (10 mL) was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate, and the organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the title compound (22 mg, 65%) as beige crystals.

Provenance & Evidence