Dimethylformamide → 2-[[(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetyl]amino]-1,3-thiazole-5-carboxamide

Participants

Reaction Conditions

Reaction Steps

(E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclohexyloxyimino-acetic acid (prepared as in Example 9, 112 mg, 0.31 mmol), N,N-diisopropylethylamine (163 μL, 0.94 mmol) and 2-amino-thiazole-5-carboxylic acid amide (54 mg, 0.38 mmol) were combined in methylene chloride (1.5 mL) and cooled to 0° C. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 mmol) was added and the cooling bath was removed. After stirring 16 h, thin layer chromatography analysis showed no reaction. N,N-dimethylformamide (1 mL) was added and the methylene chloride was removed in vacuo. The reaction mixture was stirred 20 h more then concentrated in vacuo and purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 2% methanol/chloroform) to afford (E)-2-[2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclohexyloxyimino-acetylamino]-thiazole-5-carboxylic acid amide (33 mg, 22%) as a white solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C19H21ClN4O5S2 [M+] 484.06, found 485 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.26-1.79 (m, 8H, 4×CH2), 2.00 (m, 2H, 2×CH of CH2), 3.32 (s, 3 H, SO2CH3), 4.40 (m, 1 H, OCH), 5.82 (brs, 2 H, NH2), 7.64 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.74 (d, Jm=1.5 Hz, 1 H, Ar), 7.96 (s, 1H, Ar), 8.23 (d, Jo=8.2 Hz, 1 H, Ar), 10.23 (s, 1 H, NH).

Provenance & Evidence