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-7-ylamino}-4-methyl-5-oxopyrazin-2-yl)pyridine-3-carbaldehyde

HRID 1411710Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1411710
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]3[C:12](=[O:21])[N:13]([CH3:20])[CH:14]=[C:15](B(O)O)[N:16]=3)=[CH:6][C:5]=12.Cl[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([N:29]2[CH2:40][CH2:39][N:38]3[C:31](=[CH:32][C:33]4[CH2:34][C:35]([CH3:42])([CH3:41])[CH2:36][C:37]=43)[C:30]2=[O:43])[C:24]=1[CH:44]=[O:45].C([O-])(=O)C.[K+].C(#N)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].O>[CH3:41][C:35]1([CH3:42])[CH2:34][C:33]2[CH:32]=[C:31]3[N:38]([CH2:39][CH2:40][N:29]([C:25]4[C:24]([CH:44]=[O:45])=[C:23]([C:15]5[N:16]=[C:11]([NH:10][C:7]6[CH:8]=[CH:9][N:4]7[CH:3]=[CH:2][N:1]=[C:5]7[CH:6]=6)[C:12](=[O:21])[N:13]([CH3:20])[CH:14]=5)[CH:28]=[CH:27][N:26]=4)[C:30]3=[O:43])[C:37]=2[CH2:36]1

Komponenten

7

Edukt 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 768540784-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehydeHCID 866843326-(Imidazo[1,2-a]pyridin-7-ylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-ylboronic Acid

Produkt 1

HCID 866843332-{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-7-ylamino}-4-methyl-5-oxopyrazin-2-yl)pyridine-3-carbaldehydeAusbeute 29,3 %

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 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 185b (400 mg, 1.40 mmol), 4-chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 108a (192 mg, 0.56 mmol), potassium acetate (220 mg, 2.24 mmol), acetonitrile (20 mL), and water (0.5 mL). After bubbling nitrogen through the suspension for 30 minutes, 1,1′-bis(diphenylphosphino)Ferrocenedichloropalladium(II) (49 mg, 0.054 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 (2×20 mL). The combined filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (40:1 to 10:1) to afford 185c (90 mg, 29%) as a light yellow solid. MS-ESI: [M+H]+ 549

Aufarbeitung

  1. customA 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen 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 (2×20 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 (40:1 to 10:1)

Quellen und Nachweise

ORD-Eintrag
ord-9aa7a0eb29a746e996d765e746119fa7
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921353B2

Notizen zur Reaktion

Wird geladen…