(6-Methoxypyridin-3-yl)boronic acid → 3-[4-(2-Hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one

HRID 600288Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 600288
Cl[C:2]1[N:27]=[CH:26][C:5]2[N:6]=[C:7]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][OH:25])[CH2:19][CH2:18]3)[C:8](=[O:16])[N:9]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH3:15])[C:4]=2[CH:3]=1.[CH3:28][O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][N:31]=1>O1CCOCC1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[OH:25][CH2:24][CH2:23][N:20]1[CH2:21][CH2:22][N:17]([C:7]2[C:8](=[O:16])[N:9]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH3:15])[C:4]3[CH:3]=[C:2]([C:33]4[CH:32]=[N:31][C:30]([O:29][CH3:28])=[CH:35][CH:34]=4)[N:27]=[CH:26][C:5]=3[N:6]=2)[CH2:18][CH2:19]1

Komponenten

7

Edukt 2

HCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 453800737-chloro-3-[4-(2-hydroxyethyl)piperazin-1-yl]-1-(2-propoxyethyl)-1H,2H-pyrido[3,4-b]pyrazin-2-one

Produkt 1

HCID 249632933-[4-(2-Hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 702EthanolLösungsmittelHCID 10340Sodium CarbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of 7-chloro-3-[4-(2-hydroxyethyl)piperazin-1-yl]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one (218 mg, 0.55 mmol) in 1,4-dioxane (3.0 mL) was treated with tetrakis(triphenylphosphine) palladium(0) (19 mg, 0.016 mmol, Strem) and stirred at room temperature for five minutes. A warm solution of 2-methoxy-5-pyridineboronic acid (41 mg, 0.27 mmol, Frontier) in ethanol (0.5 mL) and 2.0 M aqueous sodium carbonate 1.5 mL) were added. The mixture was refluxed for 2.0 hours, filtered hot through celite and the filtrate was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water, and the layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, concentrated under reduced pressure, and passed through a column of silica gel with 2.5% methanol/dichloromethane. Fractions were concentrated at reduced pressure and triturated with diethyl ether. The 7-(6-methoxypyridin-3-yl)-3-(piperazin-1-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one was obtained as a pink powder. 1H NMR (CDCl3) δ 8.77-8.76 (2H), 8.24 (1H), 7.64 (1H), 6.86 (1H), 4.43 (2H), 4.06-4.03 (4H), 4.00 (3H), 3.79 (2H), 3.71-3.67 (2H), 3.37 (2H), 2.78 (1H), 2.72-2.69 (4H), 2.66-2.62 (2H), 1.53-1.46 (2H), 0.78 (3H); HRMS m/z 469.2572 (calcd for M+H, 469.2558).

Aufarbeitung

  1. temperatureThe mixture was refluxed for 2.0 hours
  2. filtrationfiltered hot through celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and water
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. concentrationFractions were concentrated at reduced pressure
  11. customtriturated with diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-b74c1076c9014b58bd180696d69435d0
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902195B2

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