N,N'-Dimethylethylenediamine → HCID 57470975, compound

Participants

Reaction Conditions

Reaction Steps

The resin-bound (3-bromo-5-p-methoxybenzylphenyl)-3-pyridylamine described in Example 22 (200 mg, ca 0.12 mmol) was placed in a 50 mL glass reactor. Copper (I) iodide (0.6 mmol, 114 mg), potassium phosphate (127 mg, 0.6 mmol), toluene (5 mL), 6-nitroindole (0.6 mmol, 98 mg) and N,N′-dimethylethylenediamine (53 mg, 0.6 mmol) were added to the reactor, and the reactor was heated to 110° C. for 16 h under N2 atmosphere. After cooling the reaction mixture to room temperature, the resin was filtered, washed with THF (4×3 mL), MeOH (4×3 mL), H2O (4×3 mL), DMF (3×4 mL), THF (4×3 mL), methylene chloride (4×3 mL) and dried in vacuo. The resin was treated with 2% dimethylsulfide, 50% TFA/methylene chloride (2 mL) for 20 min in a 20 mL glass vial. The slurry of resin in cleavage cocktail was filtered through a fritted syringe to a 20 mL glass vial, washed with methylene chloride (2×1 mL), and the combined solution was evaporated by nitrogen blowing under mild heating to give the crude product which was confirmed by proton NMR and LC/MS analysis. The crude product was passed through a short pad of silica gel using 5% MeOH in methylene chloride. The combined fractions of product were concentrated, and the residue was further purified by prep SFC to obtain 3-(6-nitro-indol-1-yl)-5-(pyridin-3-ylamino)-phenol (4.3 mg, 0.012 mmol). 1H NMR (400 MHz, CD3OD) δ 8.49 (d, J=2.0, 1H), 8.01 (dd, J=8.8, 2.4, 1H), 7.7 (m, 1H), 7.33 (m, 1H), 6.80 (d, J=3.2, 1H), 6.70 (t, J=1.8, 1H), 6.66 (t, J=2.0, 1H), 6.53 (t, J=2.0, 1H).

Provenance & Evidence