Potassium Carbonate → 6'-(5-Chloropyridin-3-yl)-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine

HRID 1770988

Reaktionsgleichung

Reaktionsgleichung von HRID 1770988
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]([CH3:22])=[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.CC([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])[C:18]([CH3:22])=[N:17]5)[CH2:8][CH2:9][CH:10]([CH:13]([F:14])[F:15])[CH2:11][CH2:12]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 679795776'-Bromo-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine

Produkt 1

HCID 679793846'-(5-Chloropyridin-3-yl)-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amineAusbeute 11,2 %

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, 4H), 1.45-1.54 (m, 3H), 1.71-1.86 (m, 1H), 2.00 (dt, 1H), 2.24 (s, 3H), 2.98 (d, 1H), 3.07 (d, 1H), 5.32 (br. s., 2H), 5.64 (d, 1H), 6.86 (d, 1H), 7.38 (d, 1H), 7.50 (dd, 1H), 7.93 (t, 1H), 8.49 (d, 1H), 8.65 (d, 1H); 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-69a3ece4366e441286c6f7f22dc5b6ea
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248129B2

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