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

HRID 398665Notes

Reaction equation

HRID 398665 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]([S:44]([CH3:47])(=[O:46])=[O:45])=[CH:40][CH:39]=2)[C:35]([OH:37])=O)[CH2:32][CH2:31][CH2:30][CH2:29]1.Cl.[NH2:49][C:50]1[S:51][C:52]([Cl:55])=[CH:53][N:54]=1.N1C=CC=CC=1.Cl>C(Cl)Cl.O.C(OCC)(=O)C>[Cl:55][C:52]1[S:51][C:50]([NH:49][C:35](=[O:37])[C@@H:34]([C:38]2[CH:43]=[CH:42][C:41]([S:44]([CH3:47])(=[O:46])=[O:45])=[CH:40][CH:39]=2)[CH2:33][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)=[N:54][CH:53]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 1487432-Amino-5-chlorothiazole hydrochlorideHCID 21356244(R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)propionic acid

Product 1

HCID 59086461N-(5-chloro-thiazol-2-yl)-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamideYield 40.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (4.60 g, 17.55 mmol) in methylene chloride (50 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (3.12 g, 17.55 mmol). The reaction mixture was stirred at 0° C. for 25 min and then treated with 3-cyclopentyl-2(R)-(4-methanesulfonylphenyl)propionic acid (prepared as in Example 128, 4.00 g, 13.50 mmol). The resulting reaction mixture was stirred at 0° C. for 15 min and then allowed to warm to 25° C. where it was stirred for 30 min. The reaction mixture was then treated with a solution of 2-amino-5-chlorothiazole hydrochloride (5.77 g, 33.75 mmol) and pyridine (4.37 mL, 54.03 mmol) in methylene chloride. The resulting reaction mixture was allowed to stir at 25° C. overnight. The reaction mixture was then diluted with water (150 mL), a 1N aqueous hydrochloric acid solution (50 mL), and ethyl acetate (100 mL). The layers were separated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (2×50 mL) and 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 N-(5-chloro-thiazol-2-yl)-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide (2.24 g, 40%) as a yellow foam: mp 83-88° C. (foam to gel); [α]23589=−73.3° (c=1, chloroform); EI-HRMS m/e calcd for C18H21ClN2O3S2 (M+) 412.0682, found 412.0692.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 0° C. for 15 min
  3. temperatureto warm to 25° C. where it
  4. stirringwas stirred for 30 min
  5. customThe resulting reaction mixture
  6. stirringto stir at 25° C. overnight
  7. customThe layers were separated
  8. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (2×50 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a70500c3c3ca4277873eed5ea3846b80
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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