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Acetonitrile → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-[6-({imidazo[1,2-a]pyridin-6-yl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]pyridin-3-yl)methyl Acetate

HRID 1021923
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1021923
BrC1N=C(N[C:11]2[CH:16]=[CH:15][N:14]3[CH:17]=[CH:18][N:19]=[C:13]3[CH:12]=2)C(=O)N(C)C=1.[C:20]([O:23][CH2:24][C:25]1[C:26]([N:34]2[CH2:45][CH2:44][N:43]3[C:36](=[CH:37][C:38]4[CH2:39][C:40]([CH3:47])([CH3:46])[CH2:41][C:42]=43)[C:35]2=[O:48])=[N:27][CH:28]=[CH:29][C:30]=1B(O)O)(=[O:22])[CH3:21].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:57](#[N:59])[CH3:58]>O.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:20]([O:23][CH2:24][C:25]1[C:26]([N:34]2[CH2:45][CH2:44][N:43]3[C:36](=[CH:37][C:38]4[CH2:39][C:40]([CH3:47])([CH3:46])[CH2:41][C:42]=43)[C:35]2=[O:48])=[N:27][CH:28]=[CH:29][C:30]=1[C:57]1[N:59]=[C:36]([NH:43][C:16]2[CH:11]=[CH:12][C:13]3[N:14]([CH:17]=[CH:18][N:19]=3)[CH:15]=2)[C:35](=[O:48])[N:34]([CH3:26])[CH:58]=1)(=[O:22])[CH3:21]
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Komponenten

7

Edukt 4

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 866843315-Bromo-3-(imidazo[1,2-a]pyridin-7-ylamino)-1-methylpyrazin-2(1H)-oneHCID 86684340[4-(Dihydroxyboranyl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate

Produkt 1

HCID 86684377
(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-[6-({imidazo[1,2-a]pyridin-6-yl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]pyridin-3-yl)methyl Acetate
Ausbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 25-mL single-neck round-bottomed flask equipped with a reflux condenser was charged with 201a (64 mg, 0.20 mmol), {3-[(acetyloxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (160 mg, 0.40 mmol), Pd(dppf)Cl2 (10 mg, 0.012 mmol), K3PO4 (100 mg, 0.39 mmol), NaOAc.3H2O (60 mg, 0.44 mmol), water (6 drops), and acetonitrile (5 mL). The system was evacuated and refilled with N2. The reaction mixture was stirred at 100° 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 silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 201b (40 mg, 34%) as a yellow brown solid. MS-ESI: [M+H]+ 593.2.

Aufarbeitung

  1. customA 25-mL single-neck round-bottomed flask equipped with a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 20:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-fc8103307d0243ce9ac9e14d05bec611
Quelldatensatz
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08716274B2

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