Toluene → 6-oxo-N-(quinolin-3-yl)-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamide

Participants

Reaction Steps

To a suspension of 9,9-dimethyl-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3′,2′:4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid (Intermediate F, 50 mg, 0.18 mmol) in toluene (1 mL) is added thionyl chloride (27 μL, 0.37 mmol) and the mixture is heated at reflux. After 2 h, the mixture is cooled to room temperature and is concentrated under reduced pressure. Toluene (1 mL) is added to the residue and it is concentrated once again under reduced pressure. Toluene (2 mL) is added once more and the volume is reduced by half. 5-tert-butyl-3-aminoisoxazole (51 mg, 0.37 mmol) and N,N-diisopropylethylamine (64 μL, 0.37 mmol) are added and the reaction is stirred at room temperature for 16 h. The reaction mixture is evaporated and the residue is purified via preparative HPLC using a gradient elution from 10-75% acetonitrile/H2O with 0.1% TFA to afford the title compound (8 mg, 11%). LCMS: 396.83 (M+H+).

Provenance & Evidence