Réaction #58672

ord-c5bb5e90a98e4caabb8699a14c4d3abf

Conditions de réaction

Température
50°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    Concentrationthe reaction mixture was concentrated to dryness
  2. 2
    AutreThe residue was azeotroped with toluene
  3. 3
    workup.STIRRINGAfter stirring at room temperature overnight
  4. 4
    Lavagewashed with water and brine
  5. 5
    Séchagedried over anhydrous sodium sulfate
  6. 6
    Concentrationconcentrated to dryness

Mode opératoire

To a mixture of 1-(2-pyridyl)cyclopentanecarboxylic acid, benzyl ester-(Step A, 0.20 g, 0.71 mmol) in acetonitrile (3 mL) and water (1.5 mL) was added lithium hydroxide monohydrate (0.24 g, 5.6 mmol). After stirring at room temperature for 5 h and 50° C. overnight, the reaction mixture was concentrated to dryness. The residue was azeotroped with toluene and was suspended in methylene chloride (6 mL) and dimethylformamide (3 mL), and was added N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-amine hydrochloride (Diastereomer α, Reference Example 2, 0.40 g, 0.14 mm), 4-dimethylaminopyridine (0.10 g, 0.71 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (38 mg, 0.19 mmol). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water and brine, dried over anhydrous sodium sulfate and concentrated to dryness. N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-1-(2-pyridyl)cyclopentanecarboxamide was obtained by flash column chromatography on silica gel eluted with 15-20% ethyl acetate in hexane. 1H NMR (400 MHz, CD3OD): δ 8.52 (d, 1H), 7.77 (t, 1H), 7.48 (d, 1H), 7.35-7.08 (m, 4H), 7.00 (d, 2H), 6.94 (d, 2H), 6.68 (d, 2H), 4.20 (m, 1H), 2.80 (dd, 1H), 2.73 (m, 1H), 2.60 (m, 2H), 2.45 (m, 1H), 2.30 (m, 1H), 2.18 (m, 1H), 1.85-1.65 (m, 4H), 0.82 (d, 3H). LC-MS: m/e 433 (M+H)+ (3.2 min).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US07423067B2uspto-grants-2008_09