Acetic Acid → 2-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-1H-1,3,6-triaza-s-indacene-5,7-dione

Participants

Reaction Steps

To a solution of 5-amino-2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-6-nitro-isoindole-1,3-dione (40 mg, 0.12 mmol) in THF (6 mL) was added Raney Ni in H2O (1 mL) and cyclohexa-1,4-diene (800 μL). After it was stirred at the room temperature for 30 min, the reaction mixture was loaded directly on the top of a column and washed with CH2Cl2/MeOH/28% aqueous NH4OH (90:10:1). The residue obtained from evaporation of the wash was mixed with 4-iodo-2-methoxynicotinicaldehyde (34 mg, 0.13 mmol) and AcOH (0.5 mL) in MeOH (10 mL). The mixture was stirred at the room temperature for 64 h, concentrated under reduced pressure, mixed with 4 M HCl/dioxane (8 mL) and H2O (0.6 mL), heated at 50° C. for 1.5 h, and concentrated under reduced pressure to give a crude, which was subjected to HPLC purification to furnish a fluorescent product in TFA salt form. (R)-1-Amino-3-(2,4-dimethyl-phenoxy)-propan-2-ol (45 mg, 0.24 mmol) and Et3N (70 μL, 0.5 mmol) were added into the solution of this fluorescent product and the mixture was evaporated after 17.5 h of heating at 80° C. The residual crude was subjected to HPLC to afford the title compound in TFA salt form (7.86 mg, 9.2%). 1H NMR (DMSO-d6) δ 2.13 (s, 3H, CH3), 2.19 (s, 3H, CH3), 3.02-4.05 (16H), 4.15 (m, 1H), 5.35 (br s, 1H, OH), 5.53 (br s, 1H, OH), 6.23 (d, J=7 Hz, 1H), 6.84 (d, J=7 Hz, 1H), 6.92 (d, J=7 Hz, 1H), 6.98 (s, 1H), 7.39 (d, J=7 Hz, 1H), 7.65 (s, 1H), 8.11 (s, 1H), 9.78 (br s, 1H, NH), 10.94 (br s, 1H, NH), 11.30 (br s, 1H, NH); ESI-MS m/z 602.5 (MH+).

Provenance & Evidence