Water → 3,3-Dimethyl-6-(2-methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 717126Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 717126
[CH3:1][C:2]1[CH:3]=[C:4]([C:17]2[N:21]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH:20]=[N:19][N:18]=2)[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.Br[C:29]1[N:30]=[C:31]2[N:38]([CH2:39][CH2:40][CH:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[C:37]([CH3:48])([CH3:47])[C:36](=[O:49])[NH:35][C:32]2=[N:33][CH:34]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.C(O)(C)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:47][C:37]1([CH3:48])[C:36](=[O:49])[NH:35][C:32]2=[N:33][CH:34]=[C:29]([C:7]3[CH:6]=[CH:5][C:4]([C:17]4[N:21]([CH:22]5[CH2:27][CH2:26][CH2:25][CH2:24][O:23]5)[CH:20]=[N:19][N:18]=4)=[CH:3][C:2]=3[CH3:1])[N:30]=[C:31]2[N:38]1[CH2:39][CH2:40][CH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1

Komponenten

9

Edukt 5

HCID 962WaterHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 533752276-bromo-3,3-dimethyl-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneHCID 533752283-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazole

Produkt 1

HCID 533752293,3-Dimethyl-6-(2-methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 3776IsopropanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

3-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazole (1 equiv), 6-bromo-3,3-dimethyl-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (1 equiv), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.1 equiv), 1 M sodium carbonate in water (3 equiv), 1,4-dioxane and isopropanol were combined and the system was purged with nitrogen. The resulting mixture was stirred vigorously and heated at 100° C. for 1.5 h. The resulting mixture was cooled to room temperature, diluted with methanol and the volatiles removed under reduced pressure. The residue was partitioned between dichloromethane and water, shaken and the layers separated. The water layer was extracted with dichloromethane. The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified using flash chromatography (20-100% ethyl acetate in hexane followed by 0-10% methanol in dichloromethane) to give the desired product in 97% yield. MS (ESI) m/z 532.7 [M+1]+.

Aufarbeitung

  1. customthe system was purged with nitrogen
  2. temperatureThe resulting mixture was cooled to room temperature
  3. additiondiluted with methanol
  4. customthe volatiles removed under reduced pressure
  5. customThe residue was partitioned between dichloromethane and water
  6. stirringshaken
  7. customthe layers separated
  8. extractionThe water layer was extracted with dichloromethane
  9. dry with materialThe combined organics were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified

Quellen und Nachweise

ORD-Eintrag
ord-98ff5ae44428424faf27699a7b101bf3
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193692B2

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