Pyridine → N-(5-chloro-pyridin-2-yl)-3-cyclopentyl-2-(R)-(3,4-dichloro-phenyl)-propionamide

HRID 398499Notes

Reaction equation

HRID 398499 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][C@H:34]([C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=2)[C:35]([OH:37])=O)[CH2:32][CH2:31][CH2:30][CH2:29]1.[Cl:46][C:47]1[CH:48]=[CH:49][C:50]([NH2:53])=[N:51][CH:52]=1.N1C=CC=CC=1>C(Cl)Cl.O>[Cl:46][C:47]1[CH:48]=[CH:49][C:50]([NH:53][C:35](=[O:37])[C@@H:34]([C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=2)[CH2:33][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)=[N:51][CH:52]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 661742-Amino-5-chloropyridineHCID 67184N-bromobutanimideHCID 12069486(2R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid

Product 1

HCID 53829599N-(5-chloro-pyridin-2-yl)-3-cyclopentyl-2-(R)-(3,4-dichloro-phenyl)-propionamideYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (344 mg, 1.31 mmol) in methylene chloride (10 mL) cooled to 0° C. was treated with N-bromosuccinimide (263 mg, 1.48 mmol). The reaction solution was stirred at 0° C. for 5 min. At this time, 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)propionic acid (250 mg, 0.87 mmol) was added. The reaction was allowed to slowly warm to 25° C. over 45 min. At this time, 5-chloro-2-aminopyridine (145 mg, 1.13 mmol) and pyridine (0.11 mL, 1.31 mmol) were added to the reaction mixture. The reaction was stirred at 25° C. for 20 h. At this time, the reaction was diluted with water (10 mL) and extracted with methylene chloride (3×10 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded N-(5-chloro-pyridin-2-yl)3-cyclopentyl-2-(R)-(3,4-dichloro-phenyl)-propionamide (289 mg, 84%) as a white solid: mp 125-128° C.; [α]23589=−65.6° (c=0.16, chloroform); EI-HRMS m/e calcd for C19H19Cl3N2O (M+) 396.0563, found 396.0565.

Workup

  1. temperatureto slowly warm to 25° C. over 45 min
  2. stirringThe reaction was stirred at 25° C. for 20 h
  3. extractionextracted with methylene chloride (3×10 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-60c569d381bb47b4b0f82400dfa6a0b6
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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