Sodium Bicarbonate → 6-(4-(4-(cyanomethyl)-3-fluorophenyl)-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide

HRID 526541

Reaktionsgleichung

Br[C:2]1[CH:3]=[N:4][N:5]([C:9]2[CH:22]=[CH:21][C:12]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])=[O:14])=[CH:11][N:10]=2)[C:6]=1[O:7][CH3:8].[F:23][C:24]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[CH:26][C:25]=1[CH2:39][C:40]#[N:41].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:40]([CH2:39][C:25]1[CH:26]=[CH:27][C:28]([C:2]2[CH:3]=[N:4][N:5]([C:9]3[CH:22]=[CH:21][C:12]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])=[O:14])=[CH:11][N:10]=3)[C:6]=2[O:7][CH3:8])=[CH:29][C:24]=1[F:23])#[N:41]

Komponenten

Reaktionsbedingungen

Temperatur: 110 °C

Versuchsvorschrift

Combined 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide (50 mg, 0.135 mmol), 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetonitrile (70.7 mg, 0.271 mmol), dichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium(II) (8.83 mg, 0.014 mmol) and sodium bicarbonate (56.9 mg, 0.677 mmol) in dioxane (0.60 mL) and water (0.150 mL) was heated at 110° C. in the microwave for 40 min. Additional dichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium(II) was added (10 mg) and the reaction heated at 110° C. in the microwave for 1 h. The reaction mixture was diluted with EtOAc, concentrated onto Celite®, and purified on a 10 g NH silica gel column eluted with 0 to 100% EtOAc in hexanes to 6-(4-(4-(cyanomethyl)-3-fluorophenyl)-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide (27 mg, 47.1% yield). MS m/z 424 [M+H]+.

Aufarbeitung

concentrationconcentrated onto Celite®
custompurified on a 10 g NH silica gel column

Quellen und Nachweise

ORD-Eintrag: ord-444cef4b5dfe430fb1b697145dc2f46c
Quelldatensatz: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09345713B2

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