Sodium Cyanide → 7-Chloro-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine-8-carbonitrile

HRID 1615900Notes

Reaction equation

HRID 1615900 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:9][N:10]=[C:4]2[C:3]=1I.[C-:17]#[N:18].[Na+]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:9][N:10]=[C:4]2[C:3]=1[C:17]#[N:18]

Participants

5

Reactant 2

HCID 8929Sodium CyanideHCID 866964997-Chloro-8-iodo-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine

Product 1

HCID 580811367-Chloro-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine-8-carbonitrile

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

A 2.0-5.0 mL microwave vial was charged with 7-chloro-8-iodo-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine (50 mg, 0.139 mmol) and dissolved in DMF (1387 μl). To that stirring solution was added sodium cyanide (7.14 mg, 0.146 mmol) followed by copper(I) iodide (39.6 mg, 0.208 mmol). The vial was sealed and degassed using ultra pure argon and sonication for 2 min. The vial was then placed in a reaction block preheated to 120° C. After 2 hours, LCMS showed ˜7.5:1 (product:starting material). The mixture was diluted with EtOAc and sat'd sodium bicarbonate and the contents of the flask were transferred into a separatory funnel where the aqueous was extracted twice with EtOAc and discarded. The combined organics were washed with brine, dried with magnesium sulfate, and concentrated under reduced pressure. The crude was taken on into a coupling reaction without any further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.95 (d, J=7.3 Hz, 1H), 7.78 (s, 1H), 7.43 (d, J=7.5 Hz, 1H), 4.30 (q, J=11.0 Hz, 2H).

Workup

  1. customThe vial was sealed
  2. customdegassed
  3. custompure argon and sonication for 2 min
  4. custompreheated to 120° C
  5. additionThe mixture was diluted with EtOAc
  6. customthe contents of the flask were transferred into a separatory funnel
  7. extractionwhere the aqueous was extracted twice with EtOAc
  8. washThe combined organics were washed with brine
  9. dry with materialdried with magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe crude was taken on into a coupling reaction without any further purification

Sources & evidence

ORD record
ord-bdae359552bd486583a69a8715727c64
Source dataset
uspto-grants-2014_07
Patent number
US08765767B2

Reaction notes

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