Potassium Phosphate, Tribasic → 2,3-difluoro-5-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)pyridine

HRID 219281

Reaktionsgleichung

[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=[N:11]1.Cl[C:25]1[CH:26]=[C:27]([F:32])[C:28]([F:31])=[N:29][CH:30]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O.O1CCOCC1>[F:31][C:28]1[C:27]([F:32])=[CH:26][C:25]([C:13]2[CH:12]=[N:11][N:10]([CH2:9][CH2:8][O:7][CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)[CH:14]=2)=[CH:30][N:29]=1

Komponenten

Reaktionsbedingungen

Temperatur: 100 °C

Versuchsvorschrift

A 48 mL tube was charged with 1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (6.4 g, 19.9 mmol), 5-chloro-2,3-difluoropyridine (1.7 mL, 16.6 mmol), X-Phos (1.6 g, 3.3 mmol), Potassium phosphate (3.5 g, 16.6 mmol), PdOAc2 (0.4 g, 1.7 mmol), 1,4-dioxane (50 mL), and water (5.0 mL), flushed with argon, sealed, then heated at 100° C. for 3 hours. The mixture was concentrated and purified by MPLC, eluting with 2.5% MeOH/DCM over 40 minutes to afford 2,3-difluoro-5-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)pyridine as a clear oil which solidified upon standing at room temperature (3.1 g, 60.5% yield). LC/MS shows the product as the free alcohol. However, the structure of the product is as drawn above. MS m/z=226.2 [M+1]+. Calc'd for C15H17F2N3O2: 309.3

Aufarbeitung

customflushed with argon
customsealed
concentrationThe mixture was concentrated
custompurified by MPLC
washeluting with 2.5% MeOH/DCM over 40 minutes

Quellen und Nachweise

ORD-Eintrag: ord-d142ab24ed254972a9896c183a7702c2
Quelldatensatz: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08198448B2

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