Pyridine → N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide

HRID 854767Notes

Reaction equation

HRID 854767 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](O)=[O:14])[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][C:33]([Br:36])=[CH:32][N:31]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[Br:36][C:33]1[N:34]=[CH:35][C:30]([NH:29][C:13](=[O:14])[CH:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=2)[CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[N:31][CH:32]=1

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 5995392-Amino-5-bromopyrazineHCID 219590492-(3-Chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid

Product 1

HCID 9983551N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamideYield 70%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid (prepared as in Example 20, 470 mg, 1.36 mmol) in methylene chloride (25 mL) and N,N-dimethylformamide (1 drop) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.78 mL, 1.56 mmol) and then 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 (10 mL) and then treated with a solution of 2-amino-5-bromopyrazine (472 mg, 2.71 mmol, prepared according to Tetrahedron 1988, 44, 2977-2983) in tetrahydrofliran (20 mL) and pyridine (0.55 mL, 6.78 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 organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 40/60 hexanes/ethyl acetate) afforded N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide (477 mg, 70%) as a yellow foam: (ES)+-HRMS m/e calcd for C19H21ClBrN3O4S (M+H)+ 502.0198. found 502.0205.

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 organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0693fcc7ba8d498393d35ff3522bc6b6
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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