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

HRID 398640Notes

Reaction equation

[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([F:19])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[S:28][CH:29]=[CH:30][N:31]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([F:19])[CH:12]=2)[C:8]([NH:26][C:27]2[S:28][CH:29]=[CH:30][N:31]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 3-cyclopentyl-2-(3-fluoro-4-methoxy-phenyl)-propionic acid (400.0 mg, 1.50 mmol) in methylene chloride (5.0 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.82 mL, 1.65 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 10 min and at 25° C. for 30 min. The reaction mixture was then treated with a solution of 2-aminothiazole (331 mg, 3.30 mmol) and N,N-diisopropylethylamine (0.62 mL, 3.60 mmol) in tetrahydrofuran (7.5 mL). This solution was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3-fluoro-4-methoxy-phenyl)-N-thiazol-2-yl-propionamide (538.4 mg, 100%) as a white solid: mp 51-53° C.: EI-HRMS m/e calcd for C18H21FN2O2S (M+) 348.1307 found 348.1312.

Workup

stirringThis solution was stirred at 25° C. for 18 h
concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record: ord-843febd1f1aa4550acdf88ad593fbbbb
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06610846B1

Reaction notes

Loading…