Water → HCID 178423524, Verbindung

HRID 454326Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 454326
[CH3:1][C:2]1([CH3:39])[C:29](=[O:30])[NH:28][C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([C:16]4[N:20](C5CCCCO5)[CH:19]=[N:18][N:17]=4)=[CH:12][C:11]=3[CH3:27])[N:9]=[C:4]2[N:3]1[CH2:31][CH2:32][CH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.CC1C=C(C2N(C3CCCCO3)C=NN=2)C=CC=1B1OC(C)(C)C(C)(C)O1.BrC1N=C2N(CCC3CCOCC3)C(C)(C)C(=O)NC2=NC=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]>[CH3:1][C:2]1([CH3:39])[C:29](=[O:30])[NH:28][C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([C:16]4[NH:20][CH:19]=[N:18][N:17]=4)=[CH:12][C:11]=3[CH3:27])[N:9]=[C:4]2[N:3]1[CH2:31][CH2:32][CH:33]1[CH2:34][CH2:35][O:36][CH2:37][CH2:38]1

Komponenten

10

Edukt 6

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-triazoleHCID 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)-one

Produkt 1

HCID 178423524HCID 178423524, VerbindungAusbeute 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-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. 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-ccbdd2599e9c42a0a186f264e1417820
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08492381B2

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