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

HRID 398666

Reaction equation

HRID 398666 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])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.Br.[NH2:28][C:29]1[S:30][C:31]([Br:34])=[CH:32][N:33]=1.C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[Br:34][C:31]1[S:30][C:29]([NH:28][C:8](=[O:10])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[N:33][CH:32]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27238485-Bromothiazol-2-amine monohydrobromideHCID 120694893-Cyclopentyl-2-(4-methanesulfonyl-phenyl)propionic acid

Product 1

HCID 22315232N-(5-bromo-thiazol-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionamideYield 35%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionic acid (prepared in Example 130, 300 mg, 1.01 mmol) and dry N,N-dimethylformamide (2 drops) in methylene chloride (3 mL) was cooled to 0° C. and then treated dropwise with oxalyl chloride (115 μL, 1.32 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 1 h. The reaction mixture was concentrated in vacuo. The resulting yellow oil was dissolved in a small amount of methylene chloride and then slowly added to a solution of 2-amino-5-bromothiazole monohydrobromide (395 mg, 1.52 mmol) and triethylamine (424 μL, 3.04 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was then stirred at 25° C. for 15 h. The resulting reaction mixture was partitioned between water (50 mL) and ethyl acetate (50 mL), and the layers were separated. The aqueous layer was further extracted with ethyl acetate (50 mL). The combined organic layers were then dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded the N-(5-bromo-thiazol-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionamide (160 mg, 35%) as a tan foam: mp 73-75° C. (foam to gel); EI-HRMS m/e calcd for C18H21BrN2O3S2 (M+) 456.0177, found 456.0176.

Workup

  1. stirringstirred at 25° C. for 1 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionThe resulting yellow oil was dissolved in a small amount of methylene chloride
  4. customThe resulting reaction mixture
  5. stirringwas then stirred at 25° C. for 15 h
  6. customThe resulting reaction mixture
  7. customwas partitioned between water (50 mL) and ethyl acetate (50 mL)
  8. customthe layers were separated
  9. extractionThe aqueous layer was further extracted with ethyl acetate (50 mL)
  10. dry with materialThe combined organic layers were then dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1d42b5c9360b41d1b9d9f2a64b9861bb
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Linked notes

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