Hydrochloric Acid → HCID 25165897, compound

Participants

Reaction Steps

To a solution of (3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 450 μmol) in DCM (5 mL) under a nitrogen atmosphere was added 4M HCl in dioxane (1.7 mL, 6.8 mmol). The mixture was stirred at room temperature for 2 h. The solvent was then removed under vacuum and the residue dissolved in DCM (5 mL). DIPEA (320 μL, 1.8 mmol) and cyclobutylcarbonyl chloride (64 mg, 0.54 μmol) were added and the mixture stirred at room temperature for 16 h. The solvent was removed under vacuum and the residue dissolved in DCM, washed with saturated sodium carbonate solution and water and evaporated. The residue was purified by column chromatography (SiO2, EtOAc/hexanes) and recrystallised from methanol to yield cyclobutyl-[(3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidin-1-yl]-methanone as a white solid 82 mg, 43%). M.p.=253-255° C.; 1H NMR (400 MHz, DMSO-d6) δ: 10.80 (dd, J=8.0 and 2.0 Hz, 1H), 7.54 (dd, J=17.6 and 8.0 Hz, 1H), 7.36 (dd, J=18.0, 8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.20-7.16 (m, 2H), 7.01 (t, J=7.6 Hz, 1H), 6.93-6.88 (m, 1H), 6.86-6.81 (m, 1H), 6.76 (m, 1H), 4.10-3.87 (m, 6H), 3.52-3.29 (m, 3H), 2.82 (t, J=6.0 Hz, 2H), 2.24-2.00 (m, 6H), 1.87 (m, 1H), 1.75 (m, 1H). LCMS: m/e 424.16 [M+H].

Provenance & Evidence