4-(3-Amino-2-hydroxy-phenyl)-thiophene-2-carboxylic acid hydrobromide 51c (120 mg, 0.38 mmol) was dissolved in 2.7 mL of 1 N hydrochloric acid upon cooling by an ice-water bath, followed by dropwise addition of 0.45 mL of aqueous sodium nitrite (29 mg, 0.42 mmol). After the mixture was reacted for 20 minutes, 2-indan-5-yl-5-methyl-2,4-dihydro-pyrazol-3-one 1i (73 mg, 0.34 mmol) was added. The mixture was adjusted to pH 8 with saturated aqueous sodium bicarbonate followed by addition of 2 mL of ethanol. The reaction mixture was reacted overnight at room temperature. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was filtered and the filter cake was added to 20 mL of water. The mixture was adjusted to pH 3˜4 with concentrated hydrochloric acid and filtered. Then 5 mL of ethyl acetate was added to the filter cake and the mixture was stirred for 1 hour. The mixture was filtered and the filter cake was dried to obtain the title compound 4-{2-hydroxy-3-[N′-(1-indan-5-yl-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene)-hydrazino]-phenyl}-thiophene-2-carboxylic acid 52 (45 mg, yield 28.7%) as a yellow solid.
