Pyridine → HCID 66559575, compound

HRID 854800Notes

Reaction equation

HRID 854800 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH:19]([O:22][CH:23]=[O:24])[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.[NH2:31][C:32]1[CH:37]=[N:36][CH:35]=[CH:34][N:33]=1.N1C=CC=CC=1>C1(C)C=CC=CC=1.C(Cl)Cl.O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:12]([C:13](=[O:15])[NH:31][C:32]2[CH:37]=[N:36][CH:35]=[CH:34][N:33]=2)[CH2:16][CH:17]2[CH2:21][CH2:20][CH:19]([O:22][CH:23]=[O:24])[CH2:18]2)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chloride2×HCID 78747AminopyrazineHCID 21051847HCID 21051847, compound

Product 1

HCID 66559575HCID 66559575, compoundYield 82.2%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-formyloxy-cyclopentyl)-propionic acid (380 mg, 1.01 mmol) in toluene (10 mL) at 0° C. was treated with N,N-dimethylformamide (0.008 mL) followed by a 2.0M solution of oxalyl chloride in methylene chloride (0.75 mL). The reaction mixture was allowed to stir at 0° C. for 30 min and at 25° C. for 1.5 h. It appeared that a thick oil in the bottom of the reaction flask never solubilized. Additional methylene chloride (10 mL) was added at 25° C. followed by N;N-dimethylformamide (0.002 mL) and oxalyl chloride (0.3 mL). The reaction mixture was stirred at 25° C. for an additional 45 min and then concentrated in vacuo. The residue was dissolved in dry tetrahydrofuran (5 mL) and cooled to 0° C. This cold solution was then treated with a solution of 2-aminopyrazine (142 mg, 1.5 mmol) and pyridine (0.121 mL, 1.5 mmol) in dry tetrahydrofuran (5 mL) via a cannula. The resulting reaction mixture was stirred at 0° C. for 1 h and then diluted with methylene chloride (100 mL). The organic layer was successively washed with a 1M aqueous citric acid solution (2×100 mL), a saturated sodium bicarbonate solution 1×100 mL), and a saturated sodium chloride solution 1×100 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford formic acid 3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-2-(pyrazin-2-ylcarbamoyl)-ethyl]-cyclopentyl ester (375 mg, 82%) as an off-white solid.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. for an additional 45 min
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in dry tetrahydrofuran (5 mL)
  4. temperaturecooled to 0° C
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 0° C. for 1 h
  7. washThe organic layer was successively washed with a 1M aqueous citric acid solution (2×100 mL)
  8. dry with materialThe organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cb753b3c97174fd2970760ae3d5b4c2e
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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