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

HRID 890515Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 890515
Cl[C:2]1[CH:3]=[C:4]([N:9]2[C:13]3[C:14](=[O:31])[N:15]([C:18]4[CH:23]=[CH:22][C:21]([N:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C:25]5=[O:30])=[CH:20][CH:19]=4)[CH2:16][CH2:17][C:12]=3[C:11]([C:32]([F:35])([F:34])[F:33])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].C[C:37]([N:39](C)C)=O>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[Zn]>[F:8][C:7]1[CH:6]=[CH:5][C:4]([N:9]2[C:13]3[C:14](=[O:31])[N:15]([C:18]4[CH:19]=[CH:20][C:21]([N:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C:25]5=[O:30])=[CH:22][CH:23]=4)[CH2:16][CH2:17][C:12]=3[C:11]([C:32]([F:35])([F:34])[F:33])=[N:10]2)=[CH:3][C:2]=1[C:37]#[N:39]

Komponenten

7

Edukt 2

HCID 31374DimethylacetamideHCID 102075641-(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

Produkt 1

HCID 222500932-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]benzonitrileAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 23994ZincKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

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]pyridine-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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-e27aa3223d54428c85e77aecb9081db7
Quelldatensatz
uspto-grants-2006_02
Patentnummer
US06995172B2

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