Oxalyl chloride → HCID 22315077, compound

HRID 398604Notes

Reaction equation

HRID 398604 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.[NH2:34][C:35]1[CH:40]=[N:39][CH:38]=[CH:37][N:36]=1>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:34][C:35]2[CH:40]=[N:39][CH:38]=[CH:37][N:36]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 78747AminopyrazineHCID 81531DiisopropylethylamineHCID 27627253-cyclopentyl-2-(3,4-dichlorophenyl)propanoic Acid

Product 1

HCID 22315077HCID 22315077, compoundYield 30%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid (prepared as in Example 38A, 100 mg, 0.35 mmol) in methylene chloride (5 mL) and one drop of N,N-dimethylformamide was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.20 mL, 0.39 mmol). Gas evolution began immediately. The reaction mixture was stirred for 30 min at 0° C. After this time, the reaction mixture was treated with a solution of N,N-diisopropylethylamine (0.15 mL, 0.84 mmol) and 2-aminopyrazine (69 mg, 0.73 mmol) in tetrahydrofuran (4 mL) in one portion. The resulting reaction mixture was stirred for 16 h at 25° C. The reaction mixture was then diluted with water (10 mL) and extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-pyrazin-2-yl-propionamide (38 mg, 30%) as a yellow solid: mp 46.5-51.3° C.; EI-HRMS m/e calcd for C18H19Cl2N3O (M+) 363.0905, found 363.0907.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred for 16 h at 25° C
  3. extractionextracted with methylene chloride (3×15 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6dabfc85a8b34822ae13f93f1e3f1dbb
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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