1,1,3,3-Tetramethylguanidine → 2-(4-(6-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)propanamide

HRID 922367Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 922367
Cl.Cl.[N:3]1([CH:9]([CH3:13])[C:10]([NH2:12])=[O:11])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.CN(C)C(N(C)C)=N.F[C:23]1[N:28]=[C:27]([C:29]2[NH:38][C:37](=[O:39])[C:36]3[C:31](=[CH:32][C:33]([O:42][CH3:43])=[CH:34][C:35]=3[O:40][CH3:41])[N:30]=2)[CH:26]=[CH:25][CH:24]=1>CS(C)=O.ClCCl>[CH3:41][O:40][C:35]1[CH:34]=[C:33]([O:42][CH3:43])[CH:32]=[C:31]2[C:36]=1[C:37](=[O:39])[NH:38][C:29]([C:27]1[N:28]=[C:23]([N:6]3[CH2:7][CH2:8][N:3]([CH:9]([CH3:13])[C:10]([NH2:12])=[O:11])[CH2:4][CH2:5]3)[CH:24]=[CH:25][CH:26]=1)=[N:30]2

Komponenten

6

Edukt 3

HCID 664601,1,3,3-TetramethylguanidineHCID 545934312-(Piperazin-1-yl)propanamide dihydrochlorideHCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

Produkt 1

HCID 1362488412-(4-(6-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)propanamideAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of 2-(piperazin-1-yl)propanamide dihydrochloride (0.305 g, 1.33 mmol) in DMSO (1.5 mL), was added 1,1,3,3,-tetramethylguanidine (0.398 g, 3.45 mmol) at rt. The reaction mixture was stirred for 15 min. After that time 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.20 g, 0.664 mmol) was added as a solid in a single portion. The resulting mixture was stirred at 90° C. for 3.5 h. After that time the reaction was cooled to rt and diluted with dichloromethane (50 mL). The organic phase was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 93:7 dichloromethane/methanol) to give 2-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)propanamide (0.080 g, 28%) as a light yellow solid: mp 149-150° C.; 1H NMR (400 MHz, DMSO-d6) δ 11.05 (br s, 1H), 7.65-7.79 (m, 2H), 7.30 (s, 1H), 7.06 (d, J=8.20 Hz, 1H), 6.78 (s, 1H), 6.58 (s, 1H), 4.48 (br s, 1H), 3.91 (s, 3H), 3.86 (s, 3H), 3.64 (br s, 4H), 3.55 (br s, 2H), 2.54 (br s, 4H), 2.45 (t, 2H); ESI MS m/z 439 [M+H]+.

Aufarbeitung

  1. stirringThe resulting mixture was stirred at 90° C. for 3.5 h
  2. washThe organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography (silica gel, 93:7 dichloromethane/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-a4008fd2d49d416f83b332e3de30e65b
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278940B2

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