Pyridine → HCID 10368455, compound

HRID 719940Notes

Reaction equation

HRID 719940 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.[O:28]1[CH2:32][CH2:31][O:30][CH:29]1[CH2:33][C:34]1[N:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O>[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]([NH:40][C:37]2[CH:36]=[N:35][C:34]([CH2:33][CH:29]3[O:30][CH2:31][CH2:32][O:28]3)=[CH:39][N:38]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 21897209HCID 21897209, compound

Product 1

HCID 10368455HCID 10368455, compoundYield 47.2%

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, 160 mg, 0.48 mmol) in methylene chloride (5 mL) and N,N-dimethylformamide (2 drops) was cooled to 5° C. and then treated with oxalyl chloride (90 μL, 1.03 mmol). After 5 min, the cooling bath was removed, and the stirring was continued for 15 min. The mixture was concentrated in vacuo to dryness, and the residue was further concentrated in vacuo to dryness from benzene (15 mL). The resulting acid chloride was dissolved in methylene chloride (10 mL), cooled to 5° C., and then treated with a solution of the 5-[1,3]dioxolan-2-ylmethylpyrazin-2yl-amine (0.49 mmol) and pyridine (100 μL, 1.23 mmol) in methylene chloride (5 mL). The mixture was stirred at 5° C. for 30 min then at 25° C. for 18 h. The mixture was diluted with methylene chloride (25 mL) and washed with a saturated aqueous sodium bicarbonate solution (20 mL), a 0.5M aqueous hydrochloric acid solution (20 mL), and a saturated aqueous sodium chloride solution (20 mL). Each aqueous layer was back-extracted with a small portion of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, gradient elution with ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-[1,3]dioxolan-2-ylmethyl-pyrazin-2-yl)-propionamide (112 mg, 47%) as a colorless foam: (ES)+-HRMS m/e calcd for C23H28ClN3O5S (M+H)+ 494.1511, found 494.1517.

Workup

  1. customthe cooling bath was removed
  2. waitthe stirring was continued for 15 min
  3. concentrationThe mixture was concentrated in vacuo to dryness
  4. concentrationthe residue was further concentrated in vacuo to dryness from benzene (15 mL)
  5. dissolutionThe resulting acid chloride was dissolved in methylene chloride (10 mL)
  6. waitat 25° C. for 18 h
  7. washwashed with a saturated aqueous sodium bicarbonate solution (20 mL)
  8. extractionEach aqueous layer was back-extracted with a small portion of ethyl acetate
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. washFlash chromatography (Merck Silica gel 60, 230–400 mesh, gradient elution with ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fce95f0c83854593885120cdc9f24d09
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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