Pyridine → 3-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-N-(5-nitro-pyridin-2-yl)-propionamide

HRID 398705Notes

Reaction equation

HRID 398705 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]([S:44][CH3:45])=[C:40]([C:46]([F:49])([F:48])[F:47])[CH:39]=2)[C:35](O)=[O:36])[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:50][C:51]1[CH:56]=[CH:55][C:54]([N+:57]([O-:59])=[O:58])=[CH:53][N:52]=1.N1C=CC=CC=1>C(Cl)Cl>[CH:28]1([CH2:33][CH:34]([C:38]2[CH:43]=[CH:42][C:41]([S:44][CH3:45])=[C:40]([C:46]([F:47])([F:48])[F:49])[CH:39]=2)[C:35]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([N+:57]([O-:59])=[O:58])=[CH:53][N:52]=2)=[O:36])[CH2:29][CH2:30][CH2:31][CH2:32]1

Participants

7

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 778882-Amino-5-nitropyridineHCID 223151533-Cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-propionic acid

Product 1

HCID 223152163-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-N-(5-nitro-pyridin-2-yl)-propionamideYield 93.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (393 mg, 1.5 mmol) in methylene chloride (10.0 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (303 mg, 1.7 mmol). After stirring at 0° C. for 10 min, the reaction mixture was treated with 3-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-propionic acid (332 mg, 1.0 mmol). The reaction mixture was stirred at 0° C. for 20 min and at 25° C. for 30 min. At this time, the reaction mixture was treated with 2-amino-5-nitropyridine (290 mg, 1.5 mmol) and pyridine (0.14 mL, 1.8 mmol). The resulting reaction mixture was stirred at 25° C. for 20 h. The reaction mixture was then concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 200-400 mesh, 90/10 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-N-(5-nitro-pyridin-2-yl)-propionamide (425 mg, 60%) as an off-white solid: mp 109-110° C.; EI-HRMS m/e calcd for C21H22F3N3O3S (M+) 453.1334, found 453.1334.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 20 min and at 25° C. for 30 min
  2. customThe resulting reaction mixture
  3. stirringwas stirred at 25° C. for 20 h
  4. concentrationThe reaction mixture was then concentrated in vacuo

Sources & evidence

ORD record
ord-bd1e538f72a146eba4e155223e5b0637
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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