Pyridine → 2-(3-chloro-4-methanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-pyran-4-yl)-propionamide

HRID 854766Notes

Reaction equation

HRID 854766 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:22][CH2:21][O: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.[NH2:29][C:30]1[CH:35]=[N:34][CH:33]=[CH:32][N:31]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)[C:13]([NH:29][C:30]2[CH:35]=[N:34][CH:33]=[CH:32][N:31]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 78747AminopyrazineHCID 219590492-(3-Chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid

Product 1

HCID 219589812-(3-chloro-4-methanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-pyran-4-yl)-propionamideYield 50%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid (165 mg, 0.48 mmol) in methylene chloride (12 mL) and N,N-dimethylformamide (1 drop) cooled to 0° C. was treated dropwise with a 2.OM solution of oxalyl chloride in methylene chloride (0.27 mL, 0.55 mmol). The reaction was stirred at 0° C. for 30 min. At this time, the reaction was concentrated in vacuo to yield a light yellow oil. This oil was dissolved in tetrahydrofuran (5 mL) and then treated with a solution of 2-aminopyrazine (91 mg, 0.95 mmol) dissolved in tetrahydrofuran (10 mL) and pyridine (0.19 mL, 2.4 mmol). The reaction was then stirred at 25° C. for 16 h. At this time, the reaction was diluted with water (15 mL) and extracted with methylene chloride 3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 25/75 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-pyran-4-yl)-propionamide (100 mg, 50%) as a white foam: (ES)+-HRMS m/e calcd for C19H22ClN3O4S (M+H)+ 424.1093. found 424.1095.

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. customto yield a light yellow oil
  3. stirringThe reaction was then stirred at 25° C. for 16 h
  4. extractionextracted with methylene chloride 3×25 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c1e4330e8fd348c88fdfc878ea5ae2bc
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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