2-Aminopyrimidine → HCID 9863850, compound

HRID 1355083Notes

Reaction equation

HRID 1355083 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[N:31]=[CH:30][CH:29]=[CH:28][N:27]=1>C(Cl)Cl.CN(C)C=O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:25][C:26]2[N:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 3

HCID 79782-AminopyrimidineHCID 65578Oxalyl chlorideHCID 27627253-cyclopentyl-2-(3,4-dichlorophenyl)propanoic Acid

Product 1

HCID 9863850HCID 9863850, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 38A, 100 mg, 0.35 mmol) in methylene chloride (1 mL) was treated with 2 drops of dry N,N-dimethylformamide. The reaction mixture was cooled to 0° C. and then treated dropwise with oxalyl chloride (34 mL, 0.39 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 2 h. The reaction mixture was concentrated in vacuo. The resulting residue was dissolved in a small amount of methylene chloride and was slowly added to a cooled (0° C.) solution of 2-aminopyrimidine (67 mg, 0.70 mmol) in methylene chloride (1 mL). The resulting reaction mixture was stirred at 0° C. for 30 min and then stirred at 25° C. for 2 h. The reaction mixture was concentrated in vacuo to remove methylene chloride. The resulting residue was diluted with water and extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-pyrimidin-2-yl-propionamide (85.4 mg, 67%) as a white solid: mp 103–105° C.; EI-HRMS m/e calcd for C18H19Cl2N3O (M+) 363.0905, found 363.0915.

Workup

  1. stirringstirred at 25° C. for 2 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionThe resulting residue was dissolved in a small amount of methylene chloride
  4. additionwas slowly added to
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 0° C. for 30 min
  7. stirringstirred at 25° C. for 2 h
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. customto remove methylene chloride
  10. additionThe resulting residue was diluted with water
  11. extractionextracted with ethyl acetate (3×50 mL)
  12. washThe combined organic extracts were washed with a saturated aqueous sodium chloride solution
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5456944431d94db2a32241a53bae9230
Source dataset
uspto-grants-2007_05
Patent number
US07223868B2

Reaction notes

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