Potassium Carbonate → 2-Amino-7-(4-fluoro-2-(2-fluoropyridin-3-yl)phenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one

HRID 656561Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 656561
[NH2:1][C:2]1[N:11]=[C:10]([CH3:12])[C:9]2[C:8](=[O:13])[CH2:7][CH:6]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3Br)[CH2:5][C:4]=2[N:3]=1.[F:22][C:23]1[C:28](B(O)O)=[CH:27][CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC>[NH2:1][C:2]1[N:11]=[C:10]([CH3:12])[C:9]2[C:8](=[O:13])[CH2:7][CH:6]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[C:28]3[C:23]([F:22])=[N:24][CH:25]=[CH:26][CH:27]=3)[CH2:5][C:4]=2[N:3]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 57999028HCID 57999028, Verbindung

Produkt 1

HCID 579989472-Amino-7-(4-fluoro-2-(2-fluoropyridin-3-yl)phenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-oneAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

To a 10 mL recovery flask was added 2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one (33 mg, 0.0942 mmol, 1.0 eq.), 2-fluoropyridine-3-boronic acid (27 mg, 0.188 mmol, 2.0 eq.), DME (2 mL), potassium carbonate (2.0M aq., 94 μL, 0.188 mmol, 2.0 eq.), and palladium tetrakis triphenylphosphine (5 mg, 0.00471 mmol, 0.05 eq.). The reaction was refluxed overnight whereupon LC/MS analysis judged the reaction to be complete. The reaction mixture was filtered through Celite and concentrated to a residue. The residue was purified via preparatory-HPLC to give the product white solid (30 mg, 96%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.67 (dd, J=3.54, 1.77 Hz, 1H) 2.89 (br. s., 1H) 3.06 (t, J=12.51 Hz, 2H) 3.18 (br. s., 1H) 7.18 (dd, J=9.60, 2.78 Hz, 1H) 7.31-7.53 (m, 4H) 7.72 (dd, J=8.84, 5.81 Hz, 1H) 7.98 (ddd, J=9.79, 7.52, 1.89 Hz, 1H) 8.28 (d, J=4.80 Hz, 1H). ESI-MS: m/z 367.3 (M+H)+. ESI-MS: m/z 367.3 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction was refluxed overnight whereupon LC/MS analysis
  2. customthe reaction
  3. filtrationThe reaction mixture was filtered through Celite
  4. concentrationconcentrated to a residue
  5. customThe residue was purified via preparatory-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-2e7c3d6cae1f45bb9ab3572abb75e2b6
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071766B2

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