Hydrochloric Acid → 2-[6-(4-Iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoic acid

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Reaction Steps

The title compound was prepared from 2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoic acid methyl ester as obtained in Example 1. The ester (270 mg, 0.47 mmol) was stirred in tetrahydrofuran (1 mL) and 10% sodium hydroxide (1 mL) for 5 h. The reaction was acidified with 1N hydrochloric acid to pH 3 and extracted with ethyl acetate (3×5 mL). The combined extracts were washed with water (2×5 mL), dried over sodium sulfate, filtered, and evaporated to give 2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoic acid (263 mg, 100%) as a colorless solid. The acid (263 mg, 0.47 mmol) was dissolved in dimethylformamide (3 mL) to which were added triethylamine (233 mL, 1.68 mmol) and 3-aminopyridine (54 mg, 0.58 mmol). After 10 minutes benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent) was added and stirring continued for 24 hr. The reaction was poured into ethyl acetate/water, and the phases were separated. The aqueous was extracted twice with ethyl acetate. The combined organics were washed with water (4×) and once with brine, dried over sodium sulfate, filtered, and evaporated to give 278 mg (91%) of a light orange colored solid. The material was purified by preparative HPLC to give the title compound as a colorless solid. MS (ES+) 634.0 (M+H)+(100%).

Provenance & Evidence