Potassium Phosphate, Tribasic → 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyridin-2(1H)-one

HRID 1044411Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1044411
[OH:1][C:2]([CH3:24])([CH3:23])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][C:12]2=[O:20])=[CH:7][C:6]=1[O:21][CH3:22].Br[C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]([F:38])([F:37])[CH:34]([F:36])[F:35])=[CH:28][CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:1][C:2]([CH3:24])([CH3:23])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([C:26]3[CH:27]=[CH:28][C:29]([O:32][C:33]([F:37])([F:38])[CH:34]([F:36])[F:35])=[CH:30][CH:31]=3)=[CH:13][C:12]2=[O:20])=[CH:7][C:6]=1[O:21][CH3:22]

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 111643Benzene, 1-bromo-4-(1,1,2,2-tetrafluoroethoxy)-HCID 585802101-(4-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenyl)-2-oxo-1,2-dihydropyridin-4-ylboronic acid

Produkt 1

HCID 469112031-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyridin-2(1H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-2-oxo-1,2-dihydropyridin-4-ylboronic acid Part A (20 mg, 0.06 mmol), 1-bromo-4-(1,1,2,2-tetrafluoroethoxy)benzene (24.6 mg, 0.09 mmol), potassium phosphate, tribasic (32 mg, 0.15 mmol), and PalladiumTetrakis (4 mg, 3.00 μmol) in DMF (0.6 mL) was stirred under nitrogen at 80° C. overnight. The mixture was filtered, concentrated, and was purified using HPLC (Phen Luna Axia C18 5μ 10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA). The product was repurified using ISCO flash chromatography (silica gel/hexanes/ethyl acetate/methanol 100:0 to 0:90:10 gradient) to afford the desired product 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyridin-2(1H)-one B-6 (16.43 mg, 0.032 mmol, 54.0% yield) as a light yellow solid. LC/MS 482 (M+H)+, tR 0.92 min (method 5). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.63-7.67 (2H, m), 7.43 (1H, d, J=7.26 Hz), 7.34 (2H, d, J=8.58 Hz), 6.97-7.03 (2H, m), 6.90-6.96 (1H, m), 6.87 (1H, d, J=1.76 Hz), 6.49 (1H, dd, J=7.26, 1.98 Hz), 5.80-6.11 (1H, m), 3.89 (3H, s), 3.88 (2H, s), 1.37 (6H, s)

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. customwas purified
  4. customThe product was repurified

Quellen und Nachweise

ORD-Eintrag
ord-f584298ee375410fadfdd21fd8f5d237
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08563583B2

Notizen zur Reaktion

Wird geladen…