3′-Amino-2′-hydroxy-5′-methyl-biphenyl-3-carboxylic acid hydrochloride 11f (155 mg, 0.56 mmol) was dissolved in 1.9 mL of hydrochloric acid (1 N) upon cooling by an ice-water bath, followed by dropwise addition of 1.2 mL of aqueous sodium nitrite (42 mg, 0.61 mmol). After the mixture was stirred for 20 minutes, 5-methyl-2-(1,1,3,3-tetramethyl-indan-5-yl)-2,4-dihydro-pyrazol-3-one 19d (135 mg, 0.5 mmol) was added. The mixture was adjusted to pH 8˜9 by batch addition of aqueous sodium bicarbonate (700 mg, 8.33 mmol). The generated bubbles were quenched with 2 mL of ethanol. The reaction mixture was warmed up to room temperature and reacted overnight. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was filtered and the filter cake was dissolved in 30 mL of water. After mixing well, the mixture was adjusted to pH 3˜4 with concentrated hydrochloric acid, filtered and dried. The crude product was purified by HPLC to obtain the title compound 2′-hydroxy-5′-methyl-3′-{N′-[3-methyl-5-oxo-1-(1,1,3,3-tetramethyl-indan-5-yl)-1,5-dihydro-pyrazol-4-ylidene]-hydrazino}-biphenyl-3-carboxylic acid 20 (50 mg, yield 19.1%) as a red solid.
