Acetonitrile → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)nicotinaldehyde

HRID 1185214Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1185214
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:19]=[C:13]3[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]3[N:11]=2)=[CH:5][C:4](B(O)O)=[N:3]1.[C:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[N:46]=[CH:45][CH:44]=[C:43](Cl)[C:40]=1[CH:41]=[O:42])C=[CH:30]2)([CH3:26])([CH3:25])[CH3:24].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+].C(#[N:63])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>[C:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[N:46]=[CH:45][CH:44]=[C:43]([C:4]3[CH:5]=[C:6]([NH:9][C:10]4[CH:19]=[C:13]5[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]5[N:11]=4)[C:7](=[O:8])[N:2]([CH3:1])[N:3]=3)[C:40]=1[CH:41]=[O:42])[N:63]=[CH:30]2)([CH3:25])([CH3:26])[CH3:24]

Komponenten

8

Edukt 5

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866840631-Methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-ylboronic AcidHCID 866840642-(6-tert-butyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)-4-chloronicotinaldehyde

Produkt 1

HCID 866840622-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)nicotinaldehydeAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with 153b (200 mg, 0.66 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (240 mg, 0.66 mmol), PdCl2(dppf) (54 mg, 0.066 mmol), K3PO4 (250 mg, 1.2 mmol), sodium acetate (100 mg, 1.20 mmol), acetonitrile (10 mL), and water (0.5 mL). The system was evacuated and then refilled with N2. It was then heated at 100° C. for 1 h. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 20:1 dichloromethane/methanol to afford 153c as a pale yellow solid (170 mg, 42%). MS-ESI: [M+H]+ 584.3.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-eee625840b2a44af9080e05ad0964bd5
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669251B2

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