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

HRID 2214029Notes

Reaction equation

HRID 2214029 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:30]=[C:31]([CH:39]([CH2:43][CH:44]2[CH2:48][CH2:47][O:46][CH2:45]2)[C:40]([OH:42])=O)[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:37])=[O:36].[NH2:49][C:50]1[CH:55]=[N:54][CH:53]=[CH:52][N:51]=1.N1C=CC=CC=1>C(Cl)Cl.O>[Cl:28][C:29]1[CH:30]=[C:31]([CH:39]([CH2:43][CH:44]2[CH2:48][CH2:47][O:46][CH2:45]2)[C:40]([NH:49][C:50]2[CH:55]=[N:54][CH:53]=[CH:52][N:51]=2)=[O:42])[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:36])=[O:37]

Participants

8

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 78747AminopyrazineHCID 219590572-(3-Chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-furan-3-yl)-propionic acid

Product 1

HCID 219590132-(3-chloro-4-methanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-furan-3-yl)-propionamideYield 37.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (118 mg, 0.45 mmol) in methylene chloride (5 mL) cooled to 0° C. was treated with N-bromosuccinimide (91 mg, 0.51 mmol). Upon complete dissolution, the cooled, purple solution was then treated with 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-furan-3-yl)-propionic acid (100 mg, 0.30 mmol). The resulting reaction mixture was stirred at 0° C. for 20 min then warmed to 25° C., where it was stirred for another 30 min. The purple reaction mixture was then treated with 2-aminopyrazine (43 mg, 0.45 mmol) and pyridine (0.07 mL, 0.90 mmol) and stirred for 16 h at 25° C. The reaction was then diluted with water (10 mL) and extracted with methylene chloride (3×15 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 1.5/98.5 methylene chloride/methanol) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-furan-3-yl)-propionamide (46 mg, 37%) as a light orange foam: (ES)+-HRMS m/e calcd for C18H20ClN3O4S (M+H)+ 410.0936, found 410.0940.

Workup

  1. dissolutionUpon complete dissolution
  2. customThe resulting reaction mixture
  3. temperaturethen warmed to 25° C.
  4. stirringwhere it was stirred for another 30 min
  5. stirringstirred for 16 h at 25° C
  6. extractionextracted with methylene chloride (3×15 mL)
  7. dry with materialThe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3d2dfe888c1944679a4b024abe74c77c
Source dataset
uspto-grants-2006_09
Patent number
US07105671B2

Reaction notes

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