反应详情

A mixture of 1-methyl-4-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (19.4 mg, 0.0800 mmol), bis(tri-t-butylphosphine)palladium (3.4 mg, 0.0067 mmol), 2-[(2S)-2-(6-chloro-3-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (30.0 mg, 0.0667 mmol) and N,N-diisopropylethylamine (34.8 μL, 0.200 mmol) in 1,4-dioxane (1 mL) and water (50 μL) was microwaved at 110° C. for 15 minutes. Filtered through a pad of celite and concentrated, the residue was purified by combi-flash chromatography eluted with EtOAc/hexane (50-100%). To the purified intermediate was added methanol (0.4 mL), tetrahydrofuran (0.4 mL) and hydrazine (0.2 mL, 6 mmol). The solution was stirred at room temperature overnight. Purification by prep.—HPLC (pH=10) gave the desired product as white solid. LC-MS found: 400.1 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ ppm: 8.95 (s, 1H), 7.97 (s, 1H), 7.72 (s, 1H), 7.23 (m, 1H), 6.98 (m, 2H), 6.95 (dt, J1=9.30 Hz, J2=1.80 Hz, 1H), 4.59 (s, 2H), 4.41 (m, 1H), 3.93 (s, 3H), 3.02 (dd, J1=14.40 Hz, J2=5.10 Hz, 1H), 2.89 (m, 1H), 2.81 (d, J=6.60 Hz, 2H).

1. customwas microwaved at 110° C. for 15 minutes
2. filtrationFiltered through a pad of celite
3. concentrationconcentrated
4. customthe residue was purified by combi-flash chromatography
5. washeluted with EtOAc/hexane (50-100%)
6. customPurification by prep.—HPLC (pH=10)