反应详情

To a 5 mL microwave reaction vial were introduced 3-amino-1-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrazole-4-carbonitrile (50 mg, 0.121 mmol), 1-(4-bromophenyl)ethanone (29 mg, 0.145 mmol), Pd2(dba)3 (7.7 mg, 0.008 mmol), 2-(DICYCLOHEXYLPHOSPHINO)-3,6-DIMETHOXY-2′-4′-6′-TRI-I-PROPYL-1,1′-BIPHENYL (Brett-Phos) (9.1 mg, 0.017 mmol), cesium carbonate (59 mg, 0.181 mmol) and suspended in t-butanol (1.5 mL). The reaction vessel was inerted three times by alternating vacuum and an Ar purge, then stirred at room temperature for 5 minutes to give a heterogeneous mixture that turned color from purplish-red to reddish-orange. The reaction was heat to 100° C. (external), during which the color of the reaction mixture changed to orange after ˜2 minutes of heating. After 1.5 hr, the reaction was judged complete by TLC. The mixture was diluted with EtOAc, filtered through a pad of diatomaceous earth and bound to silica gel. The crude product was purified over silica gel using a 12 g silica gel cartridge eluting the column with a 30%-100% EtOAc/hexanes gradient to give 3-(4-Acetyl-phenylamino)-1-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrazole-4-carbonitrile (40 mg, 62%) as a white powder.

1. customTo a 5 mL microwave reaction
2. customan Ar purge
3. customto give a heterogeneous mixture that
4. temperatureThe reaction was heat to 100° C. (external)
5. customorange after ˜2 minutes
6. temperatureof heating
7. waitAfter 1.5 hr
8. filtrationfiltered through a pad of diatomaceous earth
9. customThe crude product was purified over silica gel using a 12 g silica gel cartridge
10. washeluting the column with a 30%-100% EtOAc/hexanes gradient