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Acetonitrile → 4-[1-Methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-2-[(1S,11R)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde

HRID 1411679
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1411679
C(#N)C.Cl[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([N:11]2[C:23](=[O:24])[C:22]3[N:14]([C:15]4[C@@H:16]5[CH2:25][C@H:19]([C:20]=4[CH:21]=3)[CH2:18][CH2:17]5)[CH2:13][CH2:12]2)[C:6]=1[CH:26]=[O:27].[CH3:28][N:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[C:31]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([N:51]3[CH2:56][CH2:55][N:54]([CH:57]4[CH2:60][O:59][CH2:58]4)[CH2:53][C@@H:52]3[CH3:61])=[CH:47][N:46]=2)[C:30]1=[O:62].C([O-])(=O)C.[K+]>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].O>[CH3:28][N:29]1[C:30](=[O:62])[C:31]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([N:51]3[CH2:56][CH2:55][N:54]([CH:57]4[CH2:58][O:59][CH2:60]4)[CH2:53][C@@H:52]3[CH3:61])=[CH:47][N:46]=2)=[CH:32][C:33]([C:5]2[CH:10]=[CH:9][N:8]=[C:7]([N:11]3[C:23](=[O:24])[C:22]4[N:14]([C:15]5[C@@H:16]6[CH2:25][C@H:19]([C:20]=5[CH:21]=4)[CH2:18][CH2:17]6)[CH2:13][CH2:12]3)[C:6]=2[CH:26]=[O:27])=[CH:34]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 866837011-methyl-3-((5-((2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-oneHCID 866842944-Chloro-2-[(1S,11R)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde

Produkt 1

HCID 86684304
4-[1-Methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-2-[(1S,11R)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde
Ausbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with acetonitrile (30 mL), 4-chloro-2-[(1S,11R)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde 167g (170 mg, 0.50 mmol), (S)-1-methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 130f (336 mg, 0.70 mmol), water (3 mL), and potassium acetate (147 mg, 1.5 mmol). After bubbling argon through the suspension for 30 minutes, 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (408 mg, 0.05 mmol) was added. The system was subjected to three cycles of vacuum/argon flush and heated at 80° C. for 3 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×100 ml). The combined filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (50:1 to 30:1) to afford 171a (95 mg, 29%) as a light yellow solid. MS-ESI: [M+H]+ 661.3

Aufarbeitung

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling argon through the suspension for 30 minutes
  3. customflush
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. washThe solid was washed with dichloromethane (2×100 ml)
  7. concentrationThe combined filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica-gel column chromatography
  9. washeluting with dichloromethane/methanol (50:1 to 30:1)

Quellen und Nachweise

ORD-Eintrag
ord-5d4a4ee44f674bada47a1be14f3c1652
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08921353B2

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