Sodium Bicarbonate → methyl 6-(4-(4-cyano-2-fluorophenyl)-5-methoxy-1H-pyrazol-1-yl)nicotinate

HRID 578920Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 578920
Br[C:2]1[CH:3]=[N:4][N:5]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][N:10]=2)[C:6]=1[O:7][CH3:8].[F:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1)[C:23]#[N:24].C(=O)(O)[O-].[Na+]>O1CCOCC1.O.CCOC(C)=O.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.Cl[Pd]Cl.[Fe]>[C:23]([C:22]1[CH:25]=[CH:26][C:27]([C:2]2[CH:3]=[N:4][N:5]([C:9]3[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][N:10]=3)[C:6]=2[O:7][CH3:8])=[C:20]([F:19])[CH:21]=1)#[N:24]

Komponenten

8

Edukt 3

HCID 516892Sodium BicarbonateHCID 447552103-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 117600858methyl 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)nicotinate

Produkt 1

HCID 117600638methyl 6-(4-(4-cyano-2-fluorophenyl)-5-methoxy-1H-pyrazol-1-yl)nicotinateAusbeute 88,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178454869HCID 178454869, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Combined methyl 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)nicotinate (1.0 g, 3.20 mmol), 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (1.583 g, 6.41 mmol), dichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium(II) (0.209 g, 0.320 mmol) and sodium bicarbonate (1.346 g, 16.02 mmol) in dioxane (10 mL) and water (2.5 mL) and heated at 110° C. for 30 min in the microwave. The reaction was diluted with EtOAc, concentrated on Celite® and purified on a 100 g NH column (Moritex) eluted with 10 to 80% EtOAc in hexanes to give the title compound (1.0 g) which was used without further purification. MS m/z 353 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.90 (s, 3 H) 3.92 (s, 3 H) 7.81 (dd, J=8.1, 1.8 Hz, 1 H) 7.89-7.98 (m, 2 H) 8.00 (dd, J=10.7, 1.6 Hz, 1 H) 8.09 (d, J=3.0 Hz, 1 H) 8.51 (dd, J=8.6, 2.3 Hz, 1 H) 9.08 (dd, J=2.3, 0.5 Hz, 1 H).

Aufarbeitung

  1. concentrationconcentrated on Celite®
  2. custompurified on a 100 g NH column (Moritex)
  3. washeluted with 10 to 80% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-256216a54af94861803673e67b6ab26f
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040522B2

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