Pyridine → HCID 20707084, compound

HRID 398594Notes

Reaction equation

HRID 398594 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:30]=[C:31]([CH:39]([CH2:43][CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)[C:40]([OH:42])=O)[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:37])=[O:36].[CH2:49]([O:51][C:52](=[O:61])[C:53](=[O:60])[C:54]1[N:55]=[C:56]([NH2:59])[S:57][CH:58]=1)[CH3:50].N1C=CC=CC=1>C(Cl)Cl.O>[CH2:49]([O:51][C:52](=[O:61])[C:53]([C:54]1[N:55]=[C:56]([NH:59][C:40](=[O:42])[CH:39]([C:31]2[CH:32]=[CH:33][C:34]([S:35]([CH3:38])(=[O:36])=[O:37])=[C:29]([Cl:28])[CH:30]=2)[CH2:43][CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)[S:57][CH:58]=1)=[O:60])[CH3:50]

Participants

8

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 4356513Ethyl 2-(2-Amino-4-thiazolyl)-2-oxoacetateHCID 120676542-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 20707084HCID 20707084, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (238 mg, 0.91 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (183 mg, 1.03 mmol). The reaction mixture was stirred at 0° C. until it was completely dissolved and became light purple in color. The reaction mixture was then treated with 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 92, 200 mg, 0.61 mmol) and stirred at 0° C. for 20 min and then warmed to 25° C. where it was stirred for 30 min. After such time, the reaction mixture was treated with 2-(aminothiazol-4-yl)-oxo-acetic acid ethyl ester (182 mg, 0.91 mmol) and pyridine (0.088 mL, 1.09 mmol), and the reaction mixture was stirred at 25° C. for 16 h. The reaction was then diluted with water (10 mL) and then extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 hexanes/ethyl acetate) afforded {2-[2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-thiazol-4-yl}-oxo-acetic acid ethyl ester (208 mg, 67%) as a clear colorless oil: EI-HRMS m/e calcd for C22H25ClN2O6S2 (M+) 513.0921, found 513.0919.

Workup

  1. dissolutionwas completely dissolved
  2. stirringstirred at 0° C. for 20 min
  3. temperaturewarmed to 25° C. where it
  4. stirringwas stirred for 30 min
  5. stirringthe reaction mixture was stirred at 25° C. for 16 h
  6. extractionextracted with methylene chloride (3×15 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-63d91e7e719f4a6798c1f58e1a722444
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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