Potassium Carbonate → 5-(6-cyclopropyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046203Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2046203
Br[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:16]=[C:10]3[C:9]2=[O:25])[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:32]1(B(O)O)[CH2:34][CH2:33]1>CN(C=O)C.O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:32]1([C:2]2[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][N:11]4[N:14]=[C:15]([CH2:17][O:18][C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH:16]=[C:10]4[C:9]3=[O:25])[CH:5]=[CH:4][CH:3]=2)[CH2:34][CH2:33]1

Komponenten

8

Edukt 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 86670203HCID 86670203, Verbindung

Produkt 1

HCID 679743095-(6-cyclopropyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-oneAusbeute 64,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

Tetrakis(triphenylphosphine)palladium (0) (7 mg, 0.006 mmol), was added to a stirred suspension of 5-(6-bromo-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (50 mg, 0.12 mmol), potassium carbonate (52 mg, 0.37 mmol), cyclopropylboronic acid (21.5 mg, 0.25 mmol) in a mixture of DMF (0.5 mL) and 1,4-dioxane (0.5 mL) in a sealed tube and under nitrogen. The mixture was stirred at 150° C. for 15 minutes under microwave irradiation. The mixture was diluted with water and extracted with AcOEt. The organic layer was washed with brine, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo. The product was triturated with heptane to yield 5-(6-cyclopropyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (28 mg, 62% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 0.93-1.03 (m, 4H), 1.97-2.06 (m, 1H), 4.44-4.58 (m, 4H), 5.12 (s, 2H), 6.93-7.04 (m, 4H), 7.05 (s, 1H), 7.27-7.34 (m, 2H), 7.58 (t, J=7.8 Hz, 1H), 7.74-7.80 (m, 1H).

Aufarbeitung

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvents evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo
  9. customThe product was triturated with heptane

Quellen und Nachweise

ORD-Eintrag
ord-37bf050316b5448eb2d64ccf410f99a4
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08592422B2

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