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

HRID 398574Notes

Reaction equation

[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[S:30][CH:31]=[CH:32][N:33]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]([F:19])([F:21])[F:20])[CH:12]=2)[C:8]([NH:28][C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionic acid (304 mg, 1.0 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.6 mL, 1.2 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 15 min and at 25° C. for 24 h. The reaction mixture was then treated with 2-amino-thiazole (175 mg, 1.75 mmol) and N,N-diisopropylethylamine (0.4 mL, 2.41 mmol). This solution was stirred at 25° C. for 48 h. At this time, the reaction was concentrated in vacuo. High pressure liquid chromatography (Chromegasphere SI-60, 10 μM, 60 Å, 25 cm×23 cm ID, 60/40 heptane/ethyl acetate) afforded 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-propionamide (326 mg, 84.5%) as a light yellow solid: mp 125-127° C.; EI-HRMS m/e calcd for C18H18F4N2OS (M+) 386.1076, found 386.1086.

Workup

stirringThis solution was stirred at 25° C. for 48 h
concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record: ord-af2ddb8e2c924ae1a0364167c6919470
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06610846B1

Reaction notes

Loading…