Dimethylacetamide → 2-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile

Temperatur

140 °C

Part A. 1-(3-chloro-4-fluorophenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.35 g, 0.69 mmol), Zn(CN)2 (81 mg, 0.69 mmol), Pd2(dba)3 (63 mg, 0.07 mmol), dppf (77 mg, 0.14 mmol), and Zn (9 mg, 0.14 mmol) were added to 15 mL of DMAC. The mixture was degassed under argon and stirred at 140° C. under N2 for 12 h. The reaction was cooled to rt, ethylacetate (75 mL) was added and the mixture was filtered through Celite®. The filtrate was washed with saturated NaHCO3 solution (30 mL), water (30 mL×3), and brine (20 mL). It was then dried over Na2SO4, filtered, and concentrated. The residue was purified via flash chromatography on silica gel with 10% methanol in dichloromethane to give 2-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7,-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile (0.17 g, 50% yield). LRMS (AP+): 498.2 (M+H)+. 1H NMR (CDCl3) δ 7.91-7.85 (m, 2H), 7.31 (s, 4H), 7.28-7.25 (m, 1H), 4.16 (t, 2H), 3.63-3.61 (m, 2H), 3.18 (t, 2H), 2.56 (t, 2H), 1.96-1.93 (m, 4H).

1. customThe mixture was degassed under argon
2. temperatureThe reaction was cooled to rt
3. additionethylacetate (75 mL) was added
4. filtrationthe mixture was filtered through Celite®
5. washThe filtrate was washed with saturated NaHCO3 solution (30 mL), water (30 mL×3), and brine (20 mL)
6. dry with materialIt was then dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified via flash chromatography on silica gel with 10% methanol in dichloromethane

ORD-Eintrag

ord-6fa1f02a49a647f797b24d8d9ce80836

Quelldatensatz

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07691846B2