1-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one → 4-(1-Methyl-5-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde

HRID 592560Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592560
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][N:19]=2)[C:3]1=[O:32].Cl[C:34]1[C:39]([CH:40]=[O:41])=[C:38]([N:42]2[CH2:54][CH2:53][N:45]3[C:46]4[CH2:47][CH2:48][CH2:49][CH2:50][C:51]=4[CH:52]=[C:44]3[C:43]2=[O:55])[N:37]=[CH:36][CH:35]=1>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].C1COCC1>[CH3:1][N:2]1[C:3](=[O:32])[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][N:19]=2)=[CH:5][C:6]([C:34]2[C:39]([CH:40]=[O:41])=[C:38]([N:42]3[CH2:54][CH2:53][N:45]4[C:46]5[CH2:47][CH2:48][CH2:49][CH2:50][C:51]=5[CH:52]=[C:44]4[C:43]3=[O:55])[N:37]=[CH:36][CH:35]=2)=[CH:7]1

Komponenten

5

Edukt 2

HCID 592164661-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-oneHCID 866841404-Chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde

Produkt 1

HCID 866841904-(1-Methyl-5-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehydeAusbeute 91,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a condenser was charged with 111c (450 mg, 1.26 mmol), 4-chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde 103b (413 mg, 1.26 mmol), Pd(dppf)Cl2 (102 mg, 0.126 mmol), K3PO4.3H2O (85 mg, 0.352 mmol), and THF (10 mL). After three cycles of vacuum/argon flush, the reaction mixture was heated at 100° C. for 15 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 7:1 petroleum ether/ethyl acetate to afford 111d as a yellow solid (700 mg, 63%). MS: [M+H]+ 608.

Aufarbeitung

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a condenser
  2. customAfter three cycles of vacuum/argon flush
  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 7:1 petroleum ether/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-297cbb3bdfc04c008766f04a0de6d68d
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238655B2

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