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

HRID 1935223Notes

Reaction equation

HRID 1935223 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:51][C:52]1[S:53][CH:54]=[CH:55][N:56]=1.C(N(CC)CC)C>C(Cl)Cl.O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:15][CH:16]=2)[C:8]([NH:51][C:52]2[S:53][CH:54]=[CH:55][N:56]=2)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 224679293-Cyclopentyl-2-(4-phenoxy-phenyl)propionic acid

Product 1

HCID 224678983-cyclopentyl-2-(4-phenoxy-phenyl)-N-thiazol-2-yl-propionamideYield 76.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-phenoxy-phenyl)-propionic acid (50 mg, 0.16 mmol),benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (106 mg, 0.24 mmol), and 2-aminothiazole (21 mg, 0.24 mmol) in methylene chloride (10 mL) at 25° C. was treated with triethylamine (0.067 mL, 0.48 mmol). The reaction mixture was then stirred at 25° C. for 14 h. After this time, the reaction mixture was diluted with water (10 mL) and then extracted with methylene chloride (3×10 mL). The combined organic extracts were then washed with water (1×10 mL), a 1N aqueous sodium hydroxide solution (1×10 mL), and a 1N aqueous hydrochloric acid solution (1×10 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-phenoxy-phenyl)-N-thiazol-2-yl-propionamide (48 mg, 76%) as an off-white solid: mp 154.9-155.1° C.; EI-HRMS m/e calcd for C23H24O2N2S (M+) 392.1558, found 392.1546.

Workup

  1. extractionextracted with methylene chloride (3×10 mL)
  2. washThe combined organic extracts were then washed with water (1×10 mL)
  3. dry with materialThe organic layer was then dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c53c2a4e8523470eb0dd3291c223fd1e
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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