(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 600288Notes

Reaction equation

HRID 600288 reaction equation
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

Participants

7

Reactant 2

HCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 45380073HCID 45380073, compound

Product 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

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b74c1076c9014b58bd180696d69435d0
Source dataset
uspto-grants-2011_03
Patent number
US07902195B2

Reaction notes

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