Pyridine → 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-pyrazin-2-yl-propionamide

HRID 398715Notes

Reaction equation

HRID 398715 reaction equation
[CH:1]1([CH2:6][C@H: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.[NH2:25][C:26]1[CH:31]=[N:30][CH:29]=[CH:28][N:27]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:25][C:26]2[CH:31]=[N:30][CH:29]=[CH:28][N:27]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 78747AminopyrazineHCID 12069486(2R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid

Product 1

HCID 590864533-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-pyrazin-2-yl-propionamideYield 76%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2(R)-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 54A, 200 mg, 0.70 mmol) in methylene chloride (5 mL) was cooled to 0° C. and then treated with a 2M solution of oxalyl chloride in methylene chloride (0.52 mL, 1.0 mmol) and N,N-dimethylformamide (1 drop). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of 2-aminopyrazine (133 mg, 1.4 mmol) in tetrahydrofuran (10 mL) followed by pyridine (0.28 ml, 3.5 mmol). The resulting reaction mixture was stirred at 25° C. for 16 h. 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. Biotage chromatography (FLASH 40S, Silica, 70/30 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-pyrazin-2-yl-propionamide (192 mg, 76%) as a colorless oil: [α]23589=−62.1° (c=0.095, chloroform); EI-HRMS m/e calcd for C18H19N3OCl2 (M+) 363.0905, found 363.0893.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 25° C. for 16 h
  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-de9eed46cb8244859c9413e4b8997236
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

Loading…