Sodium Acetate → [2-(1-Methyl-5-{[5-(oxetan-3-yl)-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)-6-{1-oxo-1H,2H,3H,4H,6H,7H,8H,9H-pyrazino[1,2-a]indol-2-yl}phenyl]methyl Acetate

HRID 1919114Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1919114
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:24]([O:27][CH2:28][C:29]1[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=[CH:31][C:30]=1[N:44]1[CH2:56][CH2:55][N:47]2[C:48]3[CH2:49][CH2:50][CH2:51][CH2:52][C:53]=3[CH:54]=[C:46]2[C:45]1=[O:57])(=[O:26])[CH3:25].CC([O-])=O.[Na+]>CC#N.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]>[C:24]([O:27][CH2:28][C:29]1[C:30]([N:44]2[CH2:56][CH2:55][N:47]3[C:48]4[CH2:49][CH2:50][CH2:51][CH2:52][C:53]=4[CH:54]=[C:46]3[C:45]2=[O:57])=[CH:31][CH:32]=[CH:33][C:34]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:26])[CH3:25]

Komponenten

6

Edukt 3

HCID 517045Sodium AcetateHCID 580438772-(2-(Acetoxymethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-oneHCID 580441695-bromo-1-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one

Produkt 1

HCID 58043838[2-(1-Methyl-5-{[5-(oxetan-3-yl)-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)-6-{1-oxo-1H,2H,3H,4H,6H,7H,8H,9H-pyrazino[1,2-a]indol-2-yl}phenyl]methyl AcetateAusbeute 44,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A sealed tube was charged with the mixture of 5-bromo-1-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one 252a (265 mg, 0.7 mmol),2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 114a (320 mg, 0.7 mmol), Pd(dppf)Cl2 (56 mg, 0.07 mmol), K3PO4.3H2O(367 mg, 1.4 mmol), and NaOAc (113 mg, 1.4 mmol) in CH3CN (20 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 110° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography eluting with 30:1 methylene chloride/methanol to afford 319a as a yellow solid (200 mg, 38%). MS: [M+H]+ 638.

Aufarbeitung

  1. customThe system was evacuated
  2. additionrefilled with N2
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by flash column chromatography
  7. washeluting with 30:1 methylene chloride/methanol

Quellen und Nachweise

ORD-Eintrag
ord-28409664a6f74482bc58fc4fa3c4fed3
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08618107B2

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