Potassium Iodide → HCID 86709165, compound

HRID 1851108Notes

Reaction equation

HRID 1851108 reaction equation
[CH2:1]([C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH2:2][CH3:3].C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:26][CH2:27][S:28][CH3:29].[I-].[K+]>CN(C=O)C>[CH3:29][S:28][CH2:27][CH2:26][N:5]1[C:6]2[C:11](=[C:10]([C:13]([F:15])([F:16])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH:12]=[C:4]1[CH2:1][CH2:2][CH3:3]

Participants

6

Reactant 4

HCID 4875Potassium Iodide2×HCID 10796Cesium carbonate2×HCID 109652-Chloroethyl methyl sulfide2×HCID 674051552-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 86709165HCID 86709165, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.025 g, 0.099 mmol), Cs2CO3 (0.129 g, 0.396 mmol), (2-chloroethyl)(methyl)sulfane (0.039 mL, 0.396 mmol) and potassium iodide (0.0165 g, 0.099 mmol) in DMF (2 mL) was heated at 80° C. After ˜1 h, additional Cs2CO3 (0.129 g, 0.396 mmol), (2-chloroethyl)(methyl)sulfane (0.039 mL, 0.396 mmol) and potassium iodide (0.0165 g, 0.099 mmol) were added, and heating was continued for 1 h. Upon cooling, the mixture was partitioned between EtOAc (25 mL) and water (20 mL). The organic phase was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by preparative HPLC (Phenomenex Luna column; gradient: 10-90% MeCN-water with 0.1% TFA). The fractions with product were concentrated down to the aqueous phase and then partitioned between EtOAc (25 mL) and saturated aqueous NaHCO3 solution (20 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to give 1-(2-(methylthio)ethyl)-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile: MS (ESI): m/z 327 (M+H).

Workup

  1. temperatureheating
  2. waitwas continued for 1 h
  3. temperatureUpon cooling
  4. customthe mixture was partitioned between EtOAc (25 mL) and water (20 mL)
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC (Phenomenex Luna column; gradient: 10-90% MeCN-water with 0.1% TFA)
  10. concentrationThe fractions with product were concentrated down to the aqueous phase
  11. custompartitioned between EtOAc (25 mL) and saturated aqueous NaHCO3 solution (20 mL)
  12. washThe organic phase was washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-a10cdfb75ba74b48a371fd28e5cdf058
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

Loading…