Cl.[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][N:4]=1.CC[N:12]([CH2:15][CH3:16])[CH2:13][CH3:14].CN1C(C)=[C:21]([C:24](O)=[O:25])[C:20](=[O:27])[N:19]1[C:28]1C=CC=CC=1.[CH:34]1[CH:39]=NC2N(O)N=N[C:36]=2[CH:35]=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[OH:9][C:6]1[CH:7]=[CH:8][C:3]([NH:2][C:24]([C:21]2[C:20](=[O:27])[N:19]([CH3:28])[N:12]([C:13]3[CH:14]=[CH:36][CH:35]=[CH:34][CH:39]=3)[C:15]=2[CH3:16])=[O:25])=[N:4][CH:5]=1
A suspension of 2-amino-5-hydroxypyridine hydrochloride (500 mg, 3.41 mmol) and Et3N (0.77 mL, 5.5 mmol) in DMF (8 mL) was stirred at rt for 1 hour. At the same time, to a solution of 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (0.64 g, 2.75 mmol), HOAT (449 mg, 3.3 mmol) and EDCI (0.63 g, 3.3 mmol) in DMF (8 mL) was added Et3N (0.77 mL, 5.5 mmol) drop wise. The mixture was stirred at rt for 1 hour, followed by the addition of the above prepared mixture. The reaction was heated at 60° C. for 5 hours, then cooled to rt and diluted with water (150 mL). and adjust to pH=6 with HCl (1 M). The mixture was extracted with EtOAc (20 mL×4), and the combined organic phases were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=10/1) to give the title compound as a pale yellow solid (699 mg, 78%).
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