2-Aminopyridine → 3-cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-N-pyridin-2-yl-propionamide

HRID 398538Notes

Reaction equation

HRID 398538 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]([C:44]([F:47])([F:46])[F:45])=[C:40]([F:48])[CH:39]=2)[C:35](O)=[O:36])[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=1>C(Cl)Cl>[CH:28]1([CH2:33][CH:34]([C:38]2[CH:43]=[CH:42][C:41]([C:44]([F:46])([F:45])[F:47])=[C:40]([F:48])[CH:39]=2)[C:35]([NH:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=2)=[O:36])[CH2:29][CH2:30][CH2:31][CH2:32]1

Participants

6

Reactant 4

HCID 104392-AminopyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 223151913-Cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-propionic acid

Product 1

HCID 223152953-cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-N-pyridin-2-yl-propionamideYield 45.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (312 mg, 1.19 mmol) in methylene chloride (5 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (212 mg, 1.19 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with 3-cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-propionic acid (prepared as in Example 70, 300 mg, 0.99 mmol). The resulting reaction mixture was stirred at 0° C. for 15 min and then allowed to warm to 25° C. where it was stirred for 30 min. The reaction mixture was then treated with 2-aminopyridine (205 mg, 2.18 mmol). The resulting reaction mixture was stirred at 25° C. for 3 d. The crude reaction mixture was then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate) to afford 3-cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-N-pyridin-2-yl-propionamide (171 mg, 45%) as a pale yellow foam: mp 40-44° C. (foam to gel); EI-HRMS m/e calcd for C20H20F4N2O (M+) 380.1512, found 380.1519.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 0° C. for 15 min
  3. temperatureto warm to 25° C. where it
  4. stirringwas stirred for 30 min
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 25° C. for 3 d
  7. customThe crude reaction mixture
  8. customwas then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-5f26de9f55e14e75bab0293a6ed90b04
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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