Pyridine → HCID 67482801, compound

HRID 719944Notes

Reaction equation

HRID 719944 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.[CH2:28]([O:31][C:32]1[N:33]=[CH:34][C:35]([NH2:38])=[N:36][CH:37]=1)[CH:29]=[CH2:30].N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O>[CH2:28]([O:31][C:32]1[N:33]=[CH:34][C:35]([NH:38][C:13](=[O:15])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)[CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:36][CH:37]=1)[CH:29]=[CH2:30]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 21897211HCID 21897211, compound

Product 1

HCID 67482801HCID 67482801, compoundYield 80.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
5 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 510 mg, 1.54 mmol) in methylene chloride (15 mL) and N,N-dimethylformamide (2 drops) was cooled to 5° C. and then treated with oxalyl chloride (0.27 mL, 3.09 mmol). After stirring for 5 min, the cooling bath was removed, and the stirring continued at 25° C. for 10 min. The solvents were concentrated in vacuo, the residue was dissolved in benzene (25 mL), and the solvent was concentrated in vacuo again. The resulting acid chloride was dissolved in methylene chloride (10 mL), cooled to 5° C. and then treated with a solution of 5-allyloxy-pyrazin-2-ylamine (238 mg, 1.57 mmol) and pyridine (0.32 mL, 3.96 mmol) in methylene chloride (15 mL). The mixture was further stirred at 25° C. for 16 h. The reaction mixture was then diluted with methylene chloride (25 mL) and washed with a saturated aqueous sodium bicarbonate solution (25 mL), a 0.5M aqueous hydrochloric acid solution (25 mL), and a saturated aqueous sodium chloride solution (25 mL). Each aqueous layer was back-extracted with another portion of methylene chloride (25 mL). The combined organic phases were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, eluted with increasing concentrations of ethyl acetate/hexanes) afforded N-(5-allyloxy-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide as a white foam (574 mg, 80%).

Workup

  1. customthe cooling bath was removed
  2. waitthe stirring continued at 25° C. for 10 min
  3. concentrationThe solvents were concentrated in vacuo
  4. dissolutionthe residue was dissolved in benzene (25 mL)
  5. concentrationthe solvent was concentrated in vacuo again
  6. dissolutionThe resulting acid chloride was dissolved in methylene chloride (10 mL)
  7. stirringThe mixture was further stirred at 25° C. for 16 h
  8. washwashed with a saturated aqueous sodium bicarbonate solution (25 mL)
  9. extractionEach aqueous layer was back-extracted with another portion of methylene chloride (25 mL)
  10. dry with materialThe combined organic phases were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. washFlash chromatography (Merck Silica gel 60, 230–400 mesh, eluted with increasing concentrations of ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-102316adafd847898c9453bfca7af0fb
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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