Dimethylformamide → 5-[1-[4-(1-Acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(z)-ylidene]-2-amino-thiazol-4-one

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Reaction Conditions

Reaction Steps

The suspension of 2-amino-5-[1-[4-(piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-thiazol-4-one (223 mg, 0.63 mmol, example 48) and diisopropylethyl amine(1.4 ml, 7.9 mmol) in anhydrous dichloromethane and dimethyl formamide (1:1, 8 ml) was cooled to 0° C., followed by slow addition of acetyl chloride (54 mg, 0.69 mmol) in dichloromethane (0.5 ml). The resulting solution was then warmed up to room temperature for 1 hr. Both 5-[1-[4-(1-Acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-2-amino-thiazol-4-one and N-{5-[1-[4-(1-acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-4-oxo-4,5-dihydro-thiazol-2-yl}-acetamide were obtained. Then the solution was treated with sodium hydroxide (aq., 1N, 7 ml) at room temperature for overnight. After removing the solvents, a yellow solid was collected. HPLC (YMC C18, 2%-60% CH3CN/H2O in 20 min, float rate 20 ml/min) afforded 5-[1-[4-(1-acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-2-amino-thiazol-4-one (76 mg, 30%) as light yellow solid. LC-MS m/e 397 (MH+).

Provenance & Evidence