Pyridine → HCID 22315292, compound

HRID 398600Notes

Reaction equation

HRID 398600 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([CH2:33][CH:34]([C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=2)[C:35]([OH:37])=O)[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:46][C:47]1[CH:54]=[CH:53][C:50]([C:51]#[N:52])=[CH:49][N:48]=1.N1C=CC=CC=1>C(Cl)Cl.O>[C:51]([C:50]1[CH:53]=[CH:54][C:47]([NH:46][C:35](=[O:37])[CH:34]([C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=2)[CH2:33][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)=[N:48][CH:49]=1)#[N:52]

Participants

8

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 8182602-Amino-5-cyanopyridineHCID 27627253-cyclopentyl-2-(3,4-dichlorophenyl)propanoic Acid

Product 1

HCID 22315292HCID 22315292, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (1.23 g, 4.70 mmol) in methylene chloride (26 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (948 mg, 5.33 mmol). The reaction mixture was stirred at 0° C. until it was completely dissolved and became light purple in color. The reaction mixture was then treated with 3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid (prepared as in Example 38A, 900 mg, 3.13 mmol). The reaction mixture was stirred at 0° C. for 20 min and then warmed to 25° C. where it stirred for 30 min. After such time, the reaction mixture was treated with 6-amino-nicotinonitrile (560 mg, 4.70 mmol) and pyridine (0.46 mL, 5.64 mmol), and the reaction mixture was stirred at 25° C. for 16 h. The reaction was then diluted with water (25 mL) and then extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 85/15 hexanes/ethyl acetate) afforded N-(5-cyano-pyridin-2-yl)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide (882 mg, 73%) as a pink foam: EI-HRMS m/e calcd for C20H19Cl2N3O (M+) 387.0905, found 387.0905.

Workup

  1. dissolutionwas completely dissolved
  2. stirringThe reaction mixture was stirred at 0° C. for 20 min
  3. temperaturewarmed to 25° C. where it
  4. stirringstirred for 30 min
  5. stirringthe reaction mixture was stirred at 25° C. for 16 h
  6. extractionextracted with methylene chloride (3×25 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-02fd6b16da8043ae8b2eee6e33d08d0a
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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