Potassium Cyanide → HCID 21897310, compound

HRID 719913Notes

Reaction equation

HRID 719913 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:28])[CH:10]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[C:19]([Cl:27])[CH:18]=2)[CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[N:6][CH:7]=1.[C-:29]#[N:30].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:27][C:19]1[CH:18]=[C:17]([CH:10]([CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]([NH:8][C:5]2[CH:4]=[N:3][C:2]([C:29]#[N:30])=[CH:7][N:6]=2)=[O:28])[CH:22]=[CH:21][C:20]=1[S:23]([CH3:26])(=[O:25])=[O:24]

Participants

7

Reactant 3

HCID 9032Potassium CyanideHCID 2855718-Crown-6HCID 21897386N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 21897310HCID 21897310, compoundYield 73.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (616.0 mg, 1.266 mmol), potassium cyanide (210.0 mg, 3.225 mmol), tetrakis(triphenylphosphine)palladium(0) (30.0 mg, 0.026 mmol), copper(I) iodide (605.0 mg, 3.177 mmol), and 18-crown-6 (33.0 mg, 0.125 mmol) in anhydrous N,N-dimethylformamide (6 mL) was heated at 150° C. under nitrogen. After 2.75 h, the mixture was allowed to cool to 25° C. The mixture was then concentrated to remove solvent. The residue was diluted with methylene chloride and ethyl acetate and then filtered through a pad of celite. The celite pad was then washed well with ethyl acetate and methylene chloride. The filtrate was then concentrated in vacuo and absorbed onto silica gel (Merck Silica gel 60, 230–400 mesh). Biotage chromatography (FLASH 40L, Silica, 1/3 to 1/1 ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyrazin-2-yl)-3-cyclopentyl-propionamide (402.3 mg, 73.4%) as an off-white foam: (ES)+-HRMS m/e calcd for C20H21ClN4O3S (M+H)+ 433.1096, found 433.1101.

Workup

  1. concentrationThe mixture was then concentrated
  2. customto remove solvent
  3. additionThe residue was diluted with methylene chloride and ethyl acetate
  4. filtrationfiltered through a pad of celite
  5. washThe celite pad was then washed well with ethyl acetate and methylene chloride
  6. concentrationThe filtrate was then concentrated in vacuo
  7. customabsorbed onto silica gel (Merck Silica gel 60, 230–400 mesh)

Sources & evidence

ORD record
ord-248c470bb3de49c7a6edcfcd5fa0e7a5
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

Loading…