Ethylenediamine → 5-(1H-Indol-2-yl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (1-benzyl-1H-pyrazol-4-yl)-amide

Participants

Reaction Steps

Intermediate (1d), 2-[5-(1-benzyl-1H-pyrazol-4-ylcarbamoyl)-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]indole-1-carboxylic acid tert-butyl ester (315 mg, 0.492 mmol) was stirred in tetrahydrofuran (15 mL) and 1,2-diaminoethane (89 mg, 98 ul, 1.48 mmol) was added followed by tetrabutylammonium fluoride solution 1.0M in tetrahydrofuran (2.46 mL, 2.46 mmol). The reaction mixture was heated at reflux for 18 hours, and cooled to ambient temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between water and dichloromethane, and the organic layer was separated. The aqueous was extracted with a further portion of dichloromethane and the combined dichloromethane layers were washed with water (×3) dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with dichloromethane—8% methanol/dichloromethane (gradient) to afford a solid. This solid was triturated with diethyl ether to afford the desired title compound as a yellow solid, 41 mg, 20%.

Provenance & Evidence