Sulfuric Acid → HCID 178455733, Verbindung

HRID 81210

Reaktionsgleichung

Reaktionsgleichung von HRID 81210
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.S(=O)(=O)(O)O.Cl[C:53]1[N:58]=[C:57]([C:59]2[CH:60]=[N:61][CH:62]=[C:63]([Cl:65])[CH:64]=2)[C:56]2[N:66]([CH:69]([C@H:71]3[CH2:76][CH2:75][C@H:74]([CH3:77])[CH2:73][CH2:72]3)[CH3:70])[CH:67]=[N:68][C:55]=2[CH:54]=1.[CH3:78][N:79](C)C(=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[Zn+2].[C-]#N.[Zn]>[Cl:65][C:63]1[CH:64]=[C:59]([C:57]2[C:56]3[N:66]([CH:69]([C@H:71]4[CH2:76][CH2:75][C@H:74]([CH3:77])[CH2:73][CH2:72]4)[CH3:70])[CH:67]=[N:68][C:55]=3[CH:54]=[C:53]([C:78]#[N:79])[N:58]=2)[CH:60]=[N:61][CH:62]=1

Komponenten

8

Edukt 4

HCID 1118Sulfuric AcidHCID 31374DimethylacetamideHCID 634876Binap, (A+-)-HCID 178455731HCID 178455731, Verbindung

Produkt 1

HCID 178455733HCID 178455733, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 23994ZincKatalysatorHCID 167845palladium(II) acetateKatalysator

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

In an oven-dried, nitrogen cooled flask were placed palladium(II) acetate (286 mg, 1.27 mmol) and (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (793 mg, 1.27 mmol). N,N-dimethylacetamide (76 mL) was added and degassed for three minutes with nitrogen (sparge). Sulfuric acid (0.068 mL, 1.27 mmol) was added and degassed for three minutes with nitrogen (sparge). The flask was sealed and heated to 80° C. for 30 minutes. The mixture was cooled to room temperature and added to a separate nitrogen purged flask containing racemic 6-chloro-4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine (4.96 g, 12.7 mmol), zinc cyanide (748 mg, 6.37 mmol), and zinc (83 mg, 1.27 mmol). The flask was purged with nitrogen for five minutes and sealed and heated to 80° C. for 16 hours. The reaction mixture was cooled to room temperature, filtered, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford racemic 4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C21H22ClN5 [M+H]+ 380. found 380.

Aufarbeitung

  1. customdegassed for three minutes with nitrogen (sparge)
  2. customdegassed for three minutes with nitrogen (sparge)
  3. customThe flask was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additionadded to a separate nitrogen purged flask
  6. customThe flask was purged with nitrogen for five minutes
  7. customsealed
  8. temperatureheated to 80° C. for 16 hours
  9. temperatureThe reaction mixture was cooled to room temperature
  10. filtrationfiltered
  11. additiondiluted with ethyl acetate
  12. washwashed with water and brine
  13. dry with materialThe organic layer was dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Quellen und Nachweise

ORD-Eintrag
ord-5ab78deeba3a41b8ad0e84638ffe2dd3
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846657B2

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