Dichloromethane → 6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-[1,2,3]triazolo[4,5-b]pyrazin-1-ylmethyl)-quinoline

HRID 16019Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 16019
Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)[N:9]=[N:10][C:5]2=[N:4][CH:3]=1.[O:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[O:28][CH2:29][CH2:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.C([O-])([O-])=O.[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[O:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[O:28][CH2:29][CH2:30][N:31]1[CH:35]=[C:34]([C:2]2[N:7]=[C:6]3[N:8]([CH2:11][C:12]4[CH:13]=[C:14]5[C:19](=[CH:20][CH:21]=4)[N:18]=[CH:17][CH:16]=[CH:15]5)[N:9]=[N:10][C:5]3=[N:4][CH:3]=2)[CH:33]=[N:32]1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 547756086-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinolineHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Produkt 1

HCID 593417856-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-[1,2,3]triazolo[4,5-b]pyrazin-1-ylmethyl)-quinolineAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 6-(6-bromo-[1,2,3]triazolo[4,5-b]pyrazin-1-ylmethyl)-quinoline (845 mg, 2.48 mmol) in DME (16 mL) was added 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (800 mgs, 2.48 mmol) and Cs2CO3 (2.42 g, 7.43 mmol) in H2O (4 mL). The reaction mixture was degassed and charged with nitrogen for three times. The palladium catalyst Pd(dppf).CH2Cl2 (101 mg, 0.124 mmol) was added and the reaction mixture was degassed and charged with nitrogen for three times, and stirred for 16 hours at 80° C. under nitrogen. The reaction mixture was then filtered over a pad of Celite, and washed with EtOAc (50 mL) and water (25 mL). The filtrate was extracted with EtOAc (3×50 mL). The organics were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified with a Biotage silica gel column chromatography (40+S, 0-50% EtOAc/Hexanes 5CV (column volume), 50-100% EtOAc/Hexanes 10 CV, 100% EtOAc 10 CV) to provide 6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-[1,2,3]triazolo[4,5-b]pyrazin-1-ylmethyl)-quinoline (910 mgs, 81% yield) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 9.23 (s, 1H) 8.82-8.95 (m, 1H) 8.67 (s, 1H) 8.28-8.45 (m, 2H) 7.92-8.08 (m, 2H) 7.77-7.90 (m, 1H) 7.53 (dd, J=8.29, 4.14 Hz, 1H) 6.15 (s, 2H) 4.49-4.62 (m, 2H) 4.30-4.47 (m, 2H) 3.91-4.00 (m, 1H) 3.67-3.87 (m, J=5.46 Hz, 1H) 3.47-3.60 (m, 1H) 3.35-3.42 (m, 1H) 1.48-1.66 (m, 2H) 1.32-1.45 (m, 3H).

Aufarbeitung

  1. customThe reaction mixture was degassed
  2. additioncharged with nitrogen for three times
  3. customthe reaction mixture was degassed
  4. additioncharged with nitrogen for three times
  5. filtrationThe reaction mixture was then filtered over a pad of Celite
  6. washwashed with EtOAc (50 mL) and water (25 mL)
  7. extractionThe filtrate was extracted with EtOAc (3×50 mL)
  8. dry with materialThe organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified with a Biotage silica gel column chromatography (40+S, 0-50% EtOAc/Hexanes 5CV (column volume), 50-100% EtOAc/Hexanes 10 CV, 100% EtOAc 10 CV)

Quellen und Nachweise

ORD-Eintrag
ord-2ff251583cf743d585391142946784d7
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732604B2

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