2-Bromopyridine → 1-[3-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-(pyridin-2-ylamino)-1H-pyrazole-4-carbonitrile

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 (25 mg, 0.060 mmol), 2-bromopyridine (11 mg, 0.072 mmol), Pd2(dba)3 (3.9 mg, 0.004 mmol), 2-(DICYCLOHEXYLPHOSPHINO)-3,6-DIMETHOXY-2′-4′-6′-TRI-I-PROPYL-1,1′-BIPHENYL (Brett-Phos) (4.5 mg, 0.008 mmol), cesium carbonate (29.5 mg, 0.091 mmol) and suspended in t-butanol (0.609 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 2 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 RediSep silica gel cartridge eluting the column with a 30%-100% EtOAc/hexanes gradient to give 1-[3-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-(pyridin-2-ylamino)-1H-pyrazole-4-carbonitrile (15 mg, 51%) 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 2 hr
8. filtrationfiltered through a pad of diatomaceous earth
9. customThe crude product was purified over silica gel using a 12 g RediSep silica gel cartridge
10. washeluting the column with a 30%-100% EtOAc/hexanes gradient

ORDレコード

ord-3cbcd82870a6481082c495ff2280a87d

出典データセット

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08729078B2