3′-Amino-2′-hydroxy-5′-methyl-biphenyl-3-carboxylic acid hydrochloride 11f (287 mg, 1.03 mmol) was dissolved in 3.5 mL of hydrochloric acid (1 N) upon cooling by an ice-water bath, followed by dropwise addition of 1.5 mL of aqueous sodium nitrite (78 mg, 1.13 mmol). After the mixture was stirred for 20 minutes, 2-(2,3-dihydro-benzofuran-5-yl)-5-methyl-2,4-dihydro-pyrazol-3-one 7c (200 mg, 0.93 mmol) was added. The mixture was adjusted to pH 8-9 by batch addition of aqueous sodium bicarbonate (1.298 g, 15.45 mmol). The generated bubbles were quenched with 2 mL of ethanol. The 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 then the filter cake was dissolved in 20 mL of water. After mixing well, the mixture was adjusted to pH 3˜4 with concentrated hydrochloric acid, filtered and dried. The residue was washed with 10 mL of the solvent mixture of dichloromethane/methanol (V:V=1:1), and then the crude product was purified by HPLC to obtain the title compound 3′-{N′-[1-(2,3-dihydro-benzofuran-5-yl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]-hydrazino}-2′-hydroxy-5′-methyl-biphenyl-3-carboxylic acid 13 (100 mg, yield 23.0%) as a red solid.
