反应详情

温度

93 °C

A solution of 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholin-3-one (31.9 mg, 0.105 mmol), 4-((1R,3S)-3-amino-2,2,3-trimethylcyclopentylamino)-6-bromopyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 48, 20 mg, 0.053 mmol), 1,1′-bis(di-t-butyl/diphenylphosphino) ferrocene (2.495 mg, 5.26 μmol), palladium (II) acetate (1.181 mg, 5.26 μmol) and dibasic potassium phosphate (0.079 mL, 0.158 mmol) in DMF (0.5 mL) was purged with N2 for 5 min. The reaction mixture was sealed and heated at 93° C. for 120 min. The reaction mixture was cooled and diluted with methanol and filtered. The filtrate was purified by prep HPLC [Column: YMC 20×100; Mobil phase: B in A: 20%-100% (A: 10% MeOH in H2O with 0.1% TFA, B: 90% MeOH in H2O with 0.1% TFA; gradient time: 15 min., hold time: 5 min] to afford the title compound, assumed to be TFA salt (7.2 mg, 0.012 mmol, 23.18% yield) as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 8.19 (1 H, s), 8.02 (1 H, d, J=1.54 Hz), 7.73-7.87 (2 H, m), 7.42 (2 H, d, J=8.58 Hz), 7.25 (1 H, d, J=1.54 Hz), 4.72 (1 H, t, J=9.02 Hz), 4.31 (2 H, s), 4.00-4.13 (2 H, m), 3.76-3.86 (2 H, m), 2.42-2.65 (1 H, m), 2.11-2.24 (1 H, m), 2.00-2.10 (1 H, m), 1.77-1.92 (1 H, m), 1.50 (3 H, s), 1.18 (3H, s), 1.08 (3H, s). HPLC (condition F): ret. Time 3.143 min.; LC/MS [m/z, (M+H)] 477.1.

1. customThe reaction mixture was sealed
2. temperatureThe reaction mixture was cooled
3. filtrationfiltered
4. customThe filtrate was purified by prep HPLC [Column
5. custom15 min.