Potassium Carbonate → HCID 86692168, Verbindung

HRID 539385

Reaktionsgleichung

Reaktionsgleichung von HRID 539385
Br[C:2]1[CH:24]=[C:23]2[C:5]([CH2:6][C:7]3([C:16]42[N:20]=[C:19]([NH2:21])[C:18](C)=[N:17]4)[CH2:12][CH2:11][CH:10]([CH:13]([F:15])[F:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[N:30][CH:31]=1.[CH3:35]C([PH+](C(C)(C)C)CCCS([O-])(=O)=O)(C)C.C([O-])([O-])=O.[K+].[K+]>[Na+].[Na+].Cl[Pd+2](Cl)(Cl)Cl>[Cl:25][C:26]1[CH:27]=[C:28]([C:2]2[CH:24]=[C:23]3[C:5]([CH2:6][C:7]4([C:16]53[N:20]=[C:19]([NH2:21])[CH:18]=[N:17]5)[CH2:12][CH:11]([CH3:35])[CH:10]([CH:13]([F:15])[F:14])[CH2:9][CH2:8]4)=[CH:4][CH:3]=2)[CH:29]=[N:30][CH:31]=1

Komponenten

6

Edukt 4

HCID 11430Potassium CarbonateHCID 201118775-Chloropyridine-3-boronic acidHCID 249491873-(Di-tert-butylphosphonium)propane sulfonateHCID 67979577HCID 67979577, Verbindung

Produkt 1

HCID 86692168HCID 86692168, VerbindungAusbeute 93,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178479786HCID 178479786, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

6′-Bromo-4-(difluoromethyl)-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 128, 0.1 g, 0.25 mmol), 5-chloropyridin-3-yl boronic acid (0.048 g, 0.30 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (6.77 mg, 0.03 mmol), sodium tetrachloro-palladate(II) (3.71 mg, 0.01 mmol), 2-Me THF (2 mL) and aq. K2CO3 (2.0 M, 0.379 mL, 0.76 mmol) were added to a microwave vial. The vial was sealed and evacuated and refilled with Ar (g) and then heated in the microwave reactor for 30 min at 100° C. The same amount of Pd-catalyst, ligand and boronic ester were added and the vial was sealed and evacuated and refilled with Ar (g). The vial was heated in the microwave reactor for 30 min at 100° C. EtOAc and water were added and the organic phase was extracted, dried through a phase separator and evaporated to dryness. The crude product was purified using preparative chromatography to give the title compound (12 mg, 11% yield): 1H NMR (500 MHz, CD3CN) δ ppm 1.24-1.41 (m, 4 H), 1.45-1.54 (m, 3 H), 1.71-1.86 (m, 1 H), 2.00 (dt, 1 H), 2.24 (s, 3 H), 2.98 (d, 1 H), 3.07 (d, 1 H), 5.32 (br. s., 2 H), 5.64 (d, 1 H), 6.86 (d, 1 H), 7.38 (d, 1 H), 7.50 (dd, 1 H), 7.93 (t, 1 H), 8.49 (d, 1 H), 8.65 (d, 1 H); MS (MM-ES+APCI)+m/z 429 [M+H]+.

Aufarbeitung

  1. customThe vial was sealed
  2. customevacuated
  3. additionrefilled with Ar (g)
  4. additionThe same amount of Pd-catalyst, ligand and boronic ester were added
  5. customthe vial was sealed
  6. customevacuated
  7. additionrefilled with Ar (g)
  8. temperatureThe vial was heated in the microwave reactor for 30 min at 100° C
  9. additionEtOAc and water were added
  10. extractionthe organic phase was extracted
  11. customdried through a phase separator
  12. customevaporated to dryness
  13. customThe crude product was purified

Quellen und Nachweise

ORD-Eintrag
ord-e3b0014bcfdc43dc8ee2edf67c6081e0
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865911B2

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