Potassium Carbonate → (4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

HRID 1747161Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1747161
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C@@H:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[CH3:11])[C:6]=2[CH:20]=1.C(O[C:26]([N:28]1[CH2:33][CH:32]=[C:31](B(O)O)[CH2:30][CH2:29]1)=[O:27])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:19][C:13]1[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=1[C@H:10]([N:7]1[C:6]2[CH:20]=[C:2]([C:31]3[CH2:30][CH2:29][N:28]([C:26]([C@H:29]4[CH2:30][CH2:31][CH2:32][CH2:33][NH:28]4)=[O:27])[CH2:33][CH:32]=3)[CH:3]=[CH:4][C:5]=2[N:9]=[CH:8]1)[CH3:11]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 21931462(1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acidHCID 86688429(R)-6-bromo-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole

Produkt 1

HCID 71569868(4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of (R)-6-bromo-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole (1.3 g, 3.5 mmol), (N-t-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)boronic acid pincol ester (1.2 g, 3.9 mmol), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 0.20 g, 0.18 mmol), and 2 M aqueous potassium carbonate (5.3 mL, 10.5 mmol) in toluene (10 mL) and ethanol (5 mL). The mixture was purged with nitrogen for 5 min, and then heated at 100° C. for 2 h. After cooling to room temperature, the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated in vacuo. The resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes) to afford the desired product in 90% purity (1.6 g, 3.4 mmol, 97%). MS: (ES) m/z calculated for C25H28Cl2N3O [M+H]+472.2, found 472.

Aufarbeitung

  1. customThe mixture was purged with nitrogen for 5 min
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted with ethyl acetate (20 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-012167bcad4a4c5eac6ee262c7b73581
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150550B2

Notizen zur Reaktion

Wird geladen…