2-Aminothiazole → 2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide

HRID 398436Notes

Reaction equation

HRID 398436 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl:28][C:29]1[CH:30]=[C:31]([CH:37]([CH2:41][CH:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)[C:38]([OH:40])=O)[CH:32]=[CH:33][C:34]=1[S:35][CH3:36].C(N(CC)C(C)C)(C)C.[NH2:56][C:57]1[S:58][CH:59]=[CH:60][N:61]=1>C(Cl)Cl>[Cl:28][C:29]1[CH:30]=[C:31]([CH:37]([CH2:41][CH:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)[C:38]([NH:56][C:57]2[S:58][CH:59]=[CH:60][N:61]=2)=[O:40])[CH:32]=[CH:33][C:34]=1[S:35][CH3:36]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 120676532-(3-Chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 223152092-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamideYield 71.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.62 g, 1.41 mmol) and 2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-propionic acid (0.29 g, 0.95 mmol) in methylene chloride (10 mL) was treated with N,N-diisopropylethylamine (500 μL, 2.87 mmol) and 2-aminothiazole (140 mg, 1.27 mmol). The mixture was stirred under nitrogen at 25° C. for 14 h. The reaction mixture was then washed with a 6N aqueous hydrochloric acid solution (1×15 mL) and washed with a saturated aqueous sodium chloride solution (1×25 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 4/1 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide (0.26 g, 71%) as a white solid: EI-HRMS m/e calcd for C18H21ClN2OS2 (M+) 380.0783, found 380.0792.

Workup

  1. washThe reaction mixture was then washed with a 6N aqueous hydrochloric acid solution (1×15 mL)
  2. washwashed with a saturated aqueous sodium chloride solution (1×25 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-384aefcc83f2424aa9ba47f736cf1371
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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