Pyridine → N-(5-bromo-thiazol-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 398681

Reaction equation

HRID 398681 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]([C@@H: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].Br.[NH2:50][C:51]1[S:52][C:53]([Br:56])=[CH:54][N:55]=1.N1C=CC=CC=1>C(Cl)Cl.O>[Br:56][C:53]1[S:52][C:51]([NH:50][C:40](=[O:42])[C@@H: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)=[N:55][CH:54]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 27238485-Bromothiazol-2-amine monohydrobromideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acid

Product 1

HCID 59086455N-(5-bromo-thiazol-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (595 mg, 2.27 mmol) in methylene chloride (20 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (457 mg, 2.57 mmol). The reaction mixture was stirred at 0° C. until it became homogeneous. The resulting light purple reaction mixture was then treated with 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (500 mg, 1.51 mmol). The reaction mixture was stirred at 0° C. for 20 min and then allowed to warm to 25° C. where it was stirred for 30 min. The reaction mixture was then treated with 2-amino-5-bromothiazole monohydrobromide (589 mg, 2.27 mmol) and pyridine (0.37 mL, 4.53 mmol), and then the reaction mixture was stirred at 25° C. for 16 h. The reaction was then diluted with water (15 mL) and then extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 55/45 hexanes/ethyl acetate) afforded N-(5-bromo-thiazol-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (375 mg, 51%) as a light green foam: [α]23589=−110.3° (c=0.068, chloroform); EI-HRMS m/e calcd for C18H20ClBrN2O3S2 (M+) 489.9787, found 489.9792.

Workup

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

Sources & evidence

ORD record
ord-4a70ec7974e640d5aaf98bc7e27c2810
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Linked notes

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