2-Aminopyridine → HCID 10178227, compound

HRID 1935262Notes

Reaction equation

HRID 1935262 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH3:18])[C:15]([OH:17])=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19](Cl)(=O)[C:20](Cl)=O.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1.[CH:32](N(CC)C(C)C)([CH3:34])[CH3:33]>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[CH:20]1([CH2:18][CH:14]([C:11]2[CH:10]=[CH:9][C:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:13][CH:12]=2)[C:15]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[O:17])[CH2:19][CH2:34][CH2:32][CH2:33]1

Participants

9

Reactant 4

HCID 104392-AminopyridineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 5278172-(4-Phenoxyphenyl)propionic acid

Product 1

HCID 10178227HCID 10178227, compoundYield 35%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2-(4-phenoxy-phenyl-propionic acid (prepared in Example 12A, 51 mg, 0.16 mmol) in methylene chloride (10 mL) and one drop of N,N-dimethylformamide was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.10 mL, 0.18 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of 2-aminopyridine (32 mg, 0.34 mmol) in tetrahydrofuran (2 mL) and N,N-diisopropylethylamine (0.07 mL, 0.39 mmol). The reaction mixture was stirred at 25° C. for 14 h. At this time, the reaction mixture was diluted with water (10 mL) and then extracted with methylene chloride (3×10 mL). The combined organic extracts were washed with water (1×10 mL), a 1N aqueous sodium hydroxide solution (1×10 mL), and a 1N aqueous hydrochloric acid solution (1×10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-phenoxy-phenyl)-N-pyridin-2-yl-propionamide (22 mg, 35%) as glassy solid: EI-HRMS m/e calcd for C25H26N2O2 (M+) 386.1994, found 386.2001.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. for 14 h
  2. extractionextracted with methylene chloride (3×10 mL)
  3. washThe combined organic extracts were washed with water (1×10 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8e78fd2355414b18a73a0187f98fe74a
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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