1,1,3,3-Tetramethylguanidine → 5,7-dimethoxy-2-(6-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one

HRID 922364Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 922364
F[C:2]1[N:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=3[O:19][CH3:20])[N:9]=2)[CH:5]=[CH:4][CH:3]=1.Cl.[CH3:24][S:25]([CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)(=[O:27])=[O:26].CN(C)C(N(C)C)=N>CS(C)=O.C(OCC)(=O)C>[CH3:20][O:19][C:14]1[CH:13]=[C:12]([O:21][CH3:22])[CH:11]=[C:10]2[C:15]=1[C:16](=[O:18])[NH:17][C:8]([C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([N:33]3[CH2:32][CH2:31][N:30]([CH2:29][CH2:28][S:25]([CH3:24])(=[O:26])=[O:27])[CH2:35][CH2:34]3)[N:7]=1)=[N:9]2

Komponenten

6

Edukt 3

HCID 664601,1,3,3-TetramethylguanidineHCID 666496671-[2-(Methylsulfonyl)ethyl]piperazine hydrochlorideHCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

Produkt 1

HCID 1362488345,7-dimethoxy-2-(6-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-oneAusbeute 38,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.200 g, 0.664 mmol) in DMSO (1.5 mL) under nitrogen was added 1-[2-(methylsulfonyl)ethyl]piperazine hydrochloride (0.265 g, 0.996 mmol) and 1,1,3,3-tetramethylguanidine. The reaction was stirred at 80° C. for 18 h. After that time the reaction was cooled to rt, diluted with ethyl acetate (50 mL), washed with water (2×20 mL), brine, dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 95:5 dichloromethane/methanol) to give 5,7-dimethoxy-2-(6-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one (0.120 g, 38%) as a yellow solid: mp 243-244° C.; 1H NMR (400 MHz, CDCl3): δ 10.28 (br s, 1H), 7.88 (d, J=7.3 Hz, 1H), 7.73-7.66 (m, 1H), 6.87-6.81 (m, 2H), 6.49 (d, J=2.2 Hz, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.69-3.61 (m, 4H), 3.23 (t, J=6.4 Hz, 2H), 3.09 (s, 3H), 2.98 (t, J=6.4 Hz, 2H), 2.72-2.64 (m, 4H).

Aufarbeitung

  1. temperatureAfter that time the reaction was cooled to rt
  2. washwashed with water (2×20 mL), brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe product was purified by flash column chromatography (silica gel, 95:5 dichloromethane/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-429f42d2423f4dc0bea0c90bbb3ff38f
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278940B2

Notizen zur Reaktion

Wird geladen…