Triphenylphosphine → 6-(3-(2,4-Difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

The 6-(3-(2,4-difluorophenyl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.30 g, 0.88 mmol) in THF (4 mL) was treated with tetrahydro-2H-pyran-4-ol (0.12 g, 1.1 mmol; Example #L.1.1) and Ph3P (0.35 g, 1.3 mmol). Diethyl azodicarboxylate (40 wt % in toluene, 0.52 mL, 1.32 mmol; TCI) was then added and the mixture stirred at ambient temperature for about 1 h. The reaction was concentrated under reduced pressure and then purified by silica gel chromatography using EtOAc/MeOH (stepwise gradient, 95:5 then 9:1) to isolate lower Rf major product with impurities. The material was purified further by RP-HPLC (Table 1, Method d). Concentration of the desired fractions under reduced pressure resulted in a solid that was collected by filtration and then dried to give the title compound (0.063 g, 17%) as a white solid: LC/MS (Table 1, Method a) Rt=2.40 min; MS m/z: 425.2 (M+H)+.

1. concentrationThe reaction was concentrated under reduced pressure
2. custompurified by silica gel chromatography
3. custom9:1) to isolate lower Rf major product with impurities
4. customThe material was purified further by RP-HPLC (Table 1, Method d)
5. customConcentration of the desired fractions under reduced pressure resulted in a solid
6. filtrationthat was collected by filtration
7. customdried

ORD 기록

ord-32c42d6d68dd40da883716ee27d763e4

출처 데이터셋

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08188083B2