Cesium carbonate → HCID 178455731, compound

HRID 81209

Reaction equation

HRID 81209 reaction equation
Cl[C:2]1[C:7]2[N:8]([CH:11]([C@H:13]3[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]3)[CH3:12])[CH:9]=[N:10][C:6]=2[CH:5]=[C:4]([Cl:20])[N:3]=1.[Cl:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[N:26][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:20][C:4]1[N:3]=[C:2]([C:24]2[CH:25]=[N:26][CH:27]=[C:22]([Cl:21])[CH:23]=2)[C:7]2[N:8]([CH:11]([C@H:13]3[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]3)[CH3:12])[CH:9]=[N:10][C:6]=2[CH:5]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 201118775-Chloropyridine-3-boronic acidHCID 178455732HCID 178455732, compound

Product 1

HCID 178455731HCID 178455731, compound

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
90 °C

Procedure

Racemic 4,6-dichloro-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine (Preparative Example 4.3) (5 g, 16 mmol), 5-chloropyridine-3-boronic acid (2.77 g, 17.61 mmol), cesium carbonate (15.65 g, 48 mmol), and 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride (1.17 g, 1.6 mmol) were combined in a flask that had been oven-dried and flushed with nitrogen. Dioxane (43 mL) and water (10.6 mL) were added, and the vial was capped and heated to 90° C. for 3 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water. The organic layer was washed with brine, 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 6-chloro-4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine. MS ESI calc'd. for C20H22Cl2N4 [M+H]+ 389. found 389.

Workup

  1. customthat had been oven-dried
  2. customflushed with nitrogen
  3. additionDioxane (43 mL) and water (10.6 mL) were added
  4. customthe vial was capped
  5. temperatureThe reaction mixture was cooled to room temperature
  6. additiondiluted with ethyl acetate
  7. washwashed with water
  8. washThe organic layer was washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-9ac54be2668c4c1c8fcd755f13a475d9
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Linked notes

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