Potassium Cyanide → 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyrazin-2-yl)-3-(tetrahydro-pyran-4-yl)-propionamide

HRID 2214057Notes

Reaction equation

HRID 2214057 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:29])[CH:10]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[C:20]([Cl:28])[CH:19]=2)[CH2:11][CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[N:6][CH:7]=1.[C-:30]#[N:31].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O.[Cu]I.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>[Cl:28][C:20]1[CH:19]=[C:18]([CH:10]([CH2:11][CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]([NH:8][C:5]2[CH:4]=[N:3][C:2]([C:30]#[N:31])=[CH:7][N:6]=2)=[O:29])[CH:23]=[CH:22][C:21]=1[S:24]([CH3:27])(=[O:26])=[O:25]

Participants

7

Reactant 3

HCID 9032Potassium CyanideHCID 2855718-Crown-6HCID 9983551N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide

Product 1

HCID 104788602-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyrazin-2-yl)-3-(tetrahydro-pyran-4-yl)-propionamideYield 76%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
150 °C

Procedure

A solution of N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide (prepared as in Example 21, 325 mg, 0.65 mmol) in N,N-dimethylformamide (5 mL) at 25° C. was treated with potassium cyanide (105 mg, 1.62 mmol), copper(I) iodide (307 mg, 1.62 mmol), tetrakis(triphenylphosphine)palladium(0) (22 mg, 0.02 mmol), and 18-crown-6 (25 mg, 0.09 mmol). This reaction mixture was then heated to 150° C. under argon for 5 h. At this time, the reaction was cooled to 25° C., concentrated to half the volume, and then chloroform (40 mL) was added until all the salts precipitated out of solution. The salts were removed by filtration through a pad of celite and washed with chloroform. The filtrate was then concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 30/70 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyrazin-2-yl)-3-(tetrahydro-pyran-4-yl)-propionamide (219 mg, 76%) as a white foam: (ES)+-HRMS m/e calcd for C20H21ClN4O4S (M+H)+ 449.1045, found 449.1046.

Workup

  1. temperatureAt this time, the reaction was cooled to 25° C.
  2. concentrationconcentrated to half the volume
  3. additionchloroform (40 mL) was added until all the salts
  4. customprecipitated out of solution
  5. customThe salts were removed by filtration through a pad of celite
  6. washwashed with chloroform
  7. concentrationThe filtrate was then concentrated in vacuo

Sources & evidence

ORD record
ord-b38c6d894ce848a2a54d0baddab5d78a
Source dataset
uspto-grants-2006_09
Patent number
US07105671B2

Reaction notes

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