Potassium Iodide → 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamide

HRID 719878Notes

Reaction equation

HRID 719878 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:28])[C@@H: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.[I-].[K+].C1OCCOCCOCCOCCOCC[O:33][CH2:32]1.C(N(CC)CC)C.C([SiH](CCCCCC)CCCCCC)CCCCC>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C(C2C=CC=CC=2)CCP)C=CC=CC=1>[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]([CH:32]=[O:33])=[CH:7][N:6]=2)=[O:28])[CH:22]=[CH:21][C:20]=1[S:23]([CH3:26])(=[O:25])=[O:24]

Participants

9

Reactant 5

HCID 4875Potassium IodideHCID 8471TriethylamineHCID 2855718-Crown-6HCID 76231CID 76231HCID 86593779N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 218973302-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamideYield 146.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 53436545Diphenylpropyl phosphineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 6, 5.73 g, 11.8 mmol), potassium iodide (2.2 g, 13.0 mmol), 18-crown-6 (0.62 g, 2.4 mmol), triethylamine (4.2 mL, 29.5 mmol), diphenylpropylphosphine (81 μL, 0.35 mmol), and palladium(II) acetate (80 mg, 0.35 mmol) in anhydrous N,N-dimethylformamide (95 mL) in a pressure tube was stirred under carbon monoxide at 65 psi at 25° C. for 30 min. At this time, the reaction was treated with trihexylsilane (8.42 mL, 23.6 mmol) and was stirred under carbon monoxide at 65 psi at 110° C. for 4 h. The reaction was then allowed to cool to 25° C. and was extracted with ethyl acetate (2×200 mL). The combined organic layers were successively washed with a saturated aqueous sodium bicarbonate solution (3×50 mL) and water (3×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 1/9 to 7/3 ethyl acetate/hexanes) afforded racemized 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamide (1.53 g, 30%) as a white solid.

Workup

  1. stirringwas stirred under carbon monoxide at 65 psi at 110° C. for 4 h
  2. temperatureto cool to 25° C.
  3. extractionwas extracted with ethyl acetate (2×200 mL)
  4. washThe combined organic layers were successively washed with a saturated aqueous sodium bicarbonate solution (3×50 mL) and water (3×50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-61ce86b0d7974213a9390723d025c634
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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