Potassium Cyanide → 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-cyano-pyrazin-2-yl-propionamide

HRID 719860Notes

Reaction equation

HRID 719860 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([C@@H:23]([CH3:27])[C:24]([NH2:26])=[O:25])[C:16]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)=[N:15][C:14](Br)=[CH:13][NH:12]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[C-:28]#[N:29].[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>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([C@@H:23]([CH3:27])[C:24]([NH2:26])=[O:25])[C:16]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)=[N:15][C:14]([C:28]#[N:29])=[CH:13][NH:12]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Participants

7

Reactant 3

HCID 9032Potassium CyanideHCID 2855718-Crown-6HCID 674825672(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-bromo-pyrazin-2-yl-propionamide

Product 1

HCID 674828172(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-cyano-pyrazin-2-yl-propionamideYield 83%

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 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-bromo-pyrazin-2-yl-propionamide (6.11 g, 13.5 mmol), potassium cyanide (2.27 g, 33.8 mmol), copper(I) iodide (6.43 g, 33.8 mmol), tetrakis(triphenylphosphine)palladium(0) (320 mg, 0.27 mmol), and 18-crown-6 (365 mg, 1.37 mmol) in anhydrous N,N-dimethylformamide (30 mL) was heated at 150° C. under argon. After 4 h, the mixture was allowed to cool to 25° C. The mixture was concentrated to about one-half volume and then chloroform (700 mL) was added to precipitate the copper salts. The mixture was filtered through a pad of celite, and the salts were washed with warm chloroform (2×100 mL). The filtrate was then concentrated in vacuo. Biotage chromatography (FLASH 75S, Silica, 0% to 35% gradient ethyl acetate/hexanes) afforded 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-cyano-pyrazin-2-yl-propionamide (4.49 g, 83%) as a light yellow solid: mp 229–231° C.; (ES)+-HRMS m/e calcd for C20H23N4O3S2 (M+H)+ 399.1486, found 399.1488.

Workup

  1. concentrationThe mixture was concentrated to about one-half volume
  2. additionchloroform (700 mL) was added
  3. customto precipitate the copper salts
  4. filtrationThe mixture was filtered through a pad of celite
  5. washthe salts were washed with warm chloroform (2×100 mL)
  6. concentrationThe filtrate was then concentrated in vacuo

Sources & evidence

ORD record
ord-7b8747c83ce04d7280d836810e642936
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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