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

HRID 398584Notes

Reaction equation

HRID 398584 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([C:21]([F:24])([F:23])[F:22])[CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[NH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=1>C(Cl)Cl.N1C=CC=CC=1>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:18])=[O:19])=[C:13]([C:21]([F:22])([F:23])[F:24])[CH:12]=2)[C:8]([NH:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 104392-AminopyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimide2×HCID 120695043-Cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid

Product 1

HCID 223152703-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-pyridin-2-yl propionamideYield 61.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid (73 mg, 0.2 mmol) and triphenylphosphine (79 mg, 0.3 mmol) in methylene chloride (5.0 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (60.5 mg, 0.34 mmol). After the complete addition of N-bromosuccinimide, the reaction mixture was allowed to warm to 25° C. over 30 min. The reaction mixture was then treated with 2-aminopyridine (28.2 mg, 0.3 mmol) and pyridine (1 drop). The resulting reaction mixture was stirred at 25° C. for 48 h. The reaction mixture was then diluted with methylene chloride (50 mL). The organic layer was washed with water (1×50 mL) and a saturated aqueous sodium chloride solution (2×25 mL), dried over magnesium sulfate and sodium sulfate, filtered, and concentrated in vacuo. High pressure liquid chromatography (Chromegasphere SI-60, 10 μM, 60 Å, 25 cm×23 cm ID, 50/50 heptane/ethyl acetate) afforded 3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-pyridin-2-yl propionamide (54.2 mg, 61.5%) as a white solid: mp 86-89° C.; EI-HRMS m/e calcd for C21H23F3N2O3S (M+) 440.1383, found 440.1381.

Workup

  1. customThe resulting reaction mixture
  2. washThe organic layer was washed with water (1×50 mL)
  3. dry with materiala saturated aqueous sodium chloride solution (2×25 mL), dried over magnesium sulfate and sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-828f00af00c54ff68eb93be333e71991
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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