2-Aminopyridine → 2-(4-chloro-3-nitro-phenyl)-3-cyclopentyl-N-pyridin-2-yl-propionamide

HRID 398521Notes

Reaction equation

HRID 398521 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([CH2:39][CH:40]2[CH2:44][CH2:43][CH2:42][CH2:41]2)[C:36]([OH:38])=O)=[CH:31][C:30]=1[N+:45]([O-:47])=[O:46].[NH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=1>C(Cl)Cl>[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([CH2:39][CH:40]2[CH2:44][CH2:43][CH2:42][CH2:41]2)[C:36]([NH:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=2)=[O:38])=[CH:31][C:30]=1[N+:45]([O-:47])=[O:46]

Participants

6

Reactant 4

HCID 104392-AminopyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 223152892-(4-Chloro-3-nitro-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 223152252-(4-chloro-3-nitro-phenyl)-3-cyclopentyl-N-pyridin-2-yl-propionamideYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (105 mg, 0.403 mmol) in methylene chloride (1 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (72 mg, 0.403 mmol). The reaction mixture was stirred at 0° C. for 20 min and then treated with 2-(4-chloro-3-nitro-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 64, 100 mg, 0.336 mmol). The resulting reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C. where it was stirred for 20 min. The reaction mixture was then treated with 2-aminopyridine (70 mg, 0.739 mmol). The resulting reaction mixture was stirred at 25° C. for 15 h. The crude reaction mixture was treated with a solution of hexanes/ethyl acetate (2 mL, 3:1) and then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 hexanes/ethyl acetate). The pure 2-(4-chloro-3-nitro-phenyl)-3-cyclopentyl-N-pyridin-2-yl-propionamide (60 mg, 48%) was obtained as a pale yellow foam: mp 48-52° C. (foam to gel); EI-HRMS m/e calcd for C19H20ClN3O3 (M+) 373.1193, found 373.1185.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 0° C. for 10 min
  3. temperatureto warm to 25° C. where it
  4. stirringwas stirred for 20 min
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 25° C. for 15 h
  7. customThe crude reaction mixture
  8. customdirectly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-a8a28078e65c47b0bae3ea03138aa98e
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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