[CH2:1]([O:3][C:4](=[O:18])[C:5]([C:10]([C:12]1[CH:16]=[C:15]([Cl:17])[O:14][N:13]=1)=O)=[CH:6][N:7](C)C)[CH3:2].Cl.[C:20]([NH:24]N)([CH3:23])([CH3:22])[CH3:21].C([O-])(=O)C.[Na+]>C(O)C>[CH2:1]([O:3][C:4]([C:5]1[CH:6]=[N:7][N:24]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:10]=1[C:12]1[CH:16]=[C:15]([Cl:17])[O:14][N:13]=1)=[O:18])[CH3:2]A solution of 2-(5-chloro-isoxazole-3-carbonyl)-3-dimethylamino-acrylic acid ethyl ester (294.8 mg, 1.08 mmol) in absolute ethanol (1.4 mL, 0.77M) was treated with tert-butylhydrazine hydrochloride (137.3 mg, 1.10 mmol) and sodium acetate (108.6 mg, 1.32 mmol). The resulting mixture was heated to 90° C. overnight. At this time, the reaction was cooled to 25° C. and was concentrated in vacuo. The reaction was partitioned between water (200 mL) and dichloromethane (2×50 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Biotage chromatography (40S column 60% ethyl acetate/hexanes) followed by ISCO CombiFlash (4 g column 0-20% ethyl acetate/hexanes) afforded 1-tert-butyl-5-(5-chloro-isoxazol-3-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (67.4 g, 21%) as a yellow oil.
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