Oxalyl chloride → {2-[2-(3-Chloro-phenyl)-3-cyclopentyl-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester

HRID 398462Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([CH2:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[C:9]([OH:11])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[CH2:24]([O:26][C:27](=[O:35])[CH2:28][C:29]1[N:30]=[C:31]([NH2:34])[S:32][CH:33]=1)[CH3:25].C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O>[CH2:24]([O:26][C:27](=[O:35])[CH2:28][C:29]1[N:30]=[C:31]([NH:34][C:9](=[O:11])[CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH2:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[S:32][CH:33]=1)[CH3:25]

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 2-(3-chloro-phenyl)-3-cyclopentyl-propionic acid (252 mg, 1.0 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with a 2.0M solution 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 2 h. The reaction mixture was then treated with (2-amino-thiazol-4-yl)-acetic acid ethyl ester (409 mg, 2.2 mmol) and N,N-diisopropylethylamine (0.5 mL, 2.4 mmol). This solution was stirred at 25° C. for 48 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 {2-[2-(3-chloro-phenyl)-3-cyclopentyl-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester (254 mg, 60.3%) as a white solid: mp 121-125° C.; EI-HRMS m/e calcd for C2 H25ClN2O3S (M+) 420.1274, found 420.1268.

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-dbdd0bcbb0164acea8fbad0024973bbd
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06610846B1

Reaction notes

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