Potassium Phosphate, Tribasic → 3-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-5-[1-methyl-5-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-4-carbaldehyde

HRID 1411618Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1411618
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N:10]2[CH2:21][CH2:20][N:19]3[C:12](=[CH:13][C:14]4[CH2:15][C:16]([CH3:23])([CH3:22])[CH2:17][C:18]=43)[C:11]2=[O:24])[C:7]=1[CH:8]=[O:9].[CH3:25][N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[C:28]([NH:41][C:42]2[CH:51]=[C:45]3[CH2:46][N:47]([CH3:50])[CH2:48][CH2:49][N:44]3[N:43]=2)[C:27]1=[O:52].C([O-])(=O)C.[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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(#N)C>[CH3:22][C:16]1([CH3:23])[CH2:15][C:14]2[CH:13]=[C:12]3[N:19]([CH2:20][CH2:21][N:10]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]([C:30]5[CH:29]=[C:28]([NH:41][C:42]6[CH:51]=[C:45]7[CH2:46][N:47]([CH3:50])[CH2:48][CH2:49][N:44]7[N:43]=6)[C:27](=[O:52])[N:26]([CH3:25])[CH:31]=5)[C:7]=4[CH:8]=[O:9])[C:11]3=[O:24])[C:18]=2[CH2:17]1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 866839771-Methyl-3-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866841823-Bromo-5-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-4-carbaldehyde

Produkt 1

HCID 866842653-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-5-[1-methyl-5-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-4-carbaldehydeAusbeute 49,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterKatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 3-bromo-5-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-4-carbaldehyde 107f (233 mg, 0.60 mmol), 1-methyl-3-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridin-2-one 135a (231 mg, 0.60 mmol), Pd(dppf)Cl2 (49 mg, 0.060 mmol), potassium acetate (118 mg, 1.2 mmol), K3PO4.trihydrate (320 mg, 1.2 mmol), acetonitrile (12 mL), and water (5 drops). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 2 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 150a (168 mg, 49%) as a solid. MS-ESI: [M+H]+ 567

Aufarbeitung

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 30:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-e6164cf1fb16442dabb761511206cf76
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921353B2

Notizen zur Reaktion

Wird geladen…