2-Aminothiazole → 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide

HRID 398548Notes

Reaction equation

HRID 398548 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[C:28]([C:30]1[CH:31]=[C:32]([CH:40]([CH2:44][CH:45]2[CH2:49][CH2:48][CH2:47][CH2:46]2)[C:41]([OH:43])=O)[CH:33]=[CH:34][C:35]=1[S:36]([CH3:39])(=[O:38])=[O:37])#[N:29].[NH2:50][C:51]1[S:52][CH:53]=[CH:54][N:55]=1>C(Cl)Cl>[C:28]([C:30]1[CH:31]=[C:32]([CH:40]([CH2:44][CH:45]2[CH2:46][CH2:47][CH2:48][CH2:49]2)[C:41]([NH:50][C:51]2[S:52][CH:53]=[CH:54][N:55]=2)=[O:43])[CH:33]=[CH:34][C:35]=1[S:36]([CH3:39])(=[O:38])=[O:37])#[N:29]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 120694992-(3-Cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 223151362-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamideYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (98 mg, 0.37 mmol) in methylene chloride (1 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (67 mg, 0.37 mmol). The reaction mixture was stirred at 0° C. for 15 min and then treated with 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (100 mg, 0.31 mmol). The resulting reaction mixture was stirred at 0° C. for 5 min and then allowed to warm to 25° C. where it was stirred for 30 min. The reaction mixture was then treated with 2-aminothiazole (68 mg, 0.68 mmol). The resulting reaction mixture was stirred at 25° C. for 15 h. The crude reaction mixture was then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) to afford 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide (117 mg, 93%) as a white solid: mp 145-148° C.; EI-HRMS m/e calcd for C19H21N3O3S2 (M+) 403.1024, found 403.1023.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 0° C. for 5 min
  3. temperatureto warm to 25° C. where it
  4. stirringwas stirred for 30 min
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 25° C. for 15 h
  7. customThe crude reaction mixture
  8. customwas then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-a64a9fe2b6de4fe083f3021baaa9c85f
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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