4-(3-Amino-2-hydroxy-phenyl)-thiophene-2-carboxylic acid hydrobromide 19c (120 mg, 0.38 mmol) was dissolved in 2.7 mL of 1 M hydrochloric acid upon cooling by an ice-water bath, followed by dropwise addition of 0.45 mL of sodium nitrite solution (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 sodium bicarbonate solution followed by addition of 2 mL of ethanol. The reaction mixture was reacted overnight at room temperature. 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 (Z)-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 19d (45 mg, yield 28.7%) as a yellow solid.
