Triphenylphosphine → N-(5-bromo-pyridin-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionamide

HRID 398708Notes

Reaction equation

HRID 398708 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][C:56]([Br:59])=[CH:55][N:54]=1>C(Cl)Cl.N1C=CC=CC=1>[Br:59][C:56]1[CH:57]=[CH:58][C:53]([NH:52][C:8](=[O:9])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:18])=[O:19])=[C:13]([C:21]([F:23])([F:22])[F:24])[CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[N:54][CH:55]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 706222-Amino-5-bromopyridineHCID 120695043-Cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid

Product 1

HCID 22315274N-(5-bromo-pyridin-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionamideYield 352.9%

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 (prepared as in Example 155A, 73 mg, 0.07 mmol) and triphenylphosphine (79 mg, 0.08 mmol) in methylene chloride (5.0 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (60.5 mg, 0.34 mmol). The reaction mixture was stirred at 0° C. for 15 min and at 25° C. for 30 min. At this time, reaction mixture was treated with 2-amino-5-bromopyridine (52 mg, 0.30 mmol) and a few drops of pyridine. The resulting reaction mixture was stirred at 25° C. for 18 h. The reaction mixture was then diluted with methylene chloride (50 mL). The organic phase was washed with water (1×35 mL) and a saturated aqueous sodium chloride solution (3×35 mL), dried over magnesium sulfate and sodium sulfate, treated with charcoal, filtered through a pad of celite, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 70/30 hexanes/ethyl acetate) afforded N-(5-bromo-pyridin-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionamide (128.3 mg, quant) as a white solid: mp 81-85° C.; EI-HRMS m/e calcd for C21H22BrF3N2O3S (M+) 518.0486, found 518.0489.

Workup

  1. customAt this time, reaction mixture
  2. customThe resulting reaction mixture
  3. stirringwas stirred at 25° C. for 18 h
  4. washThe organic phase was washed with water (1×35 mL)
  5. dry with materiala saturated aqueous sodium chloride solution (3×35 mL), dried over magnesium sulfate and sodium sulfate
  6. additiontreated with charcoal
  7. filtrationfiltered through a pad of celite
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-72487f8c36bb418dbd68b203cb852aa0
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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