2,6-Lutidine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-vinyl-pyrazin-2-yl)-propionamide

HRID 719955Notes

Reaction equation

HRID 719955 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[CH:34]=[N:33][C:32]([CH:35]=[CH2:36])=[CH:31][N:30]=1.N1C(C)=CC=CC=1C>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:28][C:29]2[CH:34]=[N:33][C:32]([CH:35]=[CH2:36])=[CH:31][N:30]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

9

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 218972565-Vinylpyrazin-2-amine

Product 1

HCID 674826192(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-vinyl-pyrazin-2-yl)-propionamideYield 77%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 470 mg, 1.42 mmol) in methylene chloride (7 mL) was cooled to 0° C. and then was treated with a 2.0M solution of oxalyl chloride in methylene chloride (817 μL, 1.63 mmol) and N,N-dimethylformamide (1 mL). The reaction mixture was stirred at 0° C. for 30 min, concentrated in vacuo, and azeotroped with methylene chloride (3×2 mL). The resulting oil was then dissolved in tetrahydrofuran (10 mL) at 25° C. and then treated dropwise with a solution of 2-amino-5-vinylpyrazine (207 mg, 1.71 mmol) and 2,6-lutidine (198 μL, 1.71 mmol) in tetrahydrofuran (8 mL) via an addition funnel. The resulting cloudy solution was then stirred 25° C. overnight for 16 h. After this time, the reaction was diluted with water (10 mL) and then extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 65/35 to 20/80 hexanes/ethyl acetate) afforded the 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-vinyl-pyrazin-2-yl)-propionamide (472 mg, 77%) as a light yellow solid: (ES)+-HRMS m/e calcd for C21H24ClN3O3S (M+H)+ 434.1300, found 434.1301.

Workup

  1. concentrationconcentrated in vacuo
  2. customazeotroped with methylene chloride (3×2 mL)
  3. dissolutionThe resulting oil was then dissolved in tetrahydrofuran (10 mL) at 25° C.
  4. stirringThe resulting cloudy solution was then stirred 25° C. overnight for 16 h
  5. extractionextracted with methylene chloride (3×25 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-547851ceea854b4f93eebb57ec05d070
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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