Acetamide → 3-(3-fluoro-4-((3-(tetrahydrofuran-2-yl)propyl)amino)phenyl)-2,6-dimethyl-pyrimidin-4(3H)-one

HRID 56221

Reaktionsgleichung

Reaktionsgleichung von HRID 56221
[F:1][C:2]1[CH:3]=[C:4]([NH:17][C:18](=[O:23])[CH2:19][C:20](=O)[CH3:21])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH2:10][CH2:11][CH:12]1[CH2:16][CH2:15][CH2:14][O:13]1.[C:24]([NH2:27])(=O)[CH3:25].C1(C)C(C)=CC=CC=1.[NH4+].[Cl-]>C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.[Ti+4].C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([N:17]2[C:18](=[O:23])[CH:19]=[C:20]([CH3:21])[N:27]=[C:24]2[CH3:25])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH2:10][CH2:11][CH:12]1[CH2:16][CH2:15][CH2:14][O:13]1

Komponenten

7

Edukt 4

HCID 178AcetamideHCID 7237O-XyleneHCID 25517Ammonium ChlorideHCID 90022774N-(3-fluoro-4-((3-(tetrahydrofuran-2-yl)propyl)amino)phenyl)-3-oxobutan-amide

Produkt 1

HCID 900229363-(3-fluoro-4-((3-(tetrahydrofuran-2-yl)propyl)amino)phenyl)-2,6-dimethyl-pyrimidin-4(3H)-oneAusbeute 29,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11026Titanium isopropoxideKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
165 °C

Versuchsvorschrift

A mixture of N-(3-fluoro-4-((3-(tetrahydrofuran-2-yl)propyl)amino)phenyl)-3-oxobutanamide (250 mg, 0.78 mmol), acetamide (92 mg, 1.56 mmol), titanium tetraisopropanolate (1.9 mL) and xylene (10 mL) was stirred at 165° C. for 24 h. The mixture was then cooled to rt. 60 mL of toluene and 60 mL of saturated NH4Cl aqueous solution were added and the resulting mixture was stirred further at rt overnight. The mixture was then filtered and the filtrate was extracted with DCM (15 mL×3). The combined organic layers were washed with brine (15 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:2) to give the title compound as a yellow solid (80 mg, 29%). The compound was characterized by the following spectroscopic data:

Aufarbeitung

  1. temperatureThe mixture was then cooled to rt
  2. stirringthe resulting mixture was stirred further at rt overnight
  3. filtrationThe mixture was then filtered
  4. extractionthe filtrate was extracted with DCM (15 mL×3)
  5. washThe combined organic layers were washed with brine (15 mL×2)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:2)

Quellen und Nachweise

ORD-Eintrag
ord-3dbf39e8ebda4244a9c3ea891f60787c
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434695B2

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