Sulfuric Acid → HCID 178455733, compound

HRID 1852817Notes

Reaction equation

HRID 1852817 reaction equation
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

Participants

8

Reactant 4

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

Product 1

HCID 178455733HCID 178455733, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-e4cf6a9937c843b6bb73e7baa1138da4
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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