4-Methylmorpholine → N-[2-(6-Bromo-2H-pyrazolo[4,3-b]pyridin-2-yl)-1-cyano-1-methylethyl]-2-fluoro-4-trifluoromethoxybenzamide

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Reaction Steps

2-Fluoro-4-trifluoromethoxybenzoic acid (80 mg, 0.357 mmole), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC.HCl, 78 mg, 0.4 mmole), 1-hydroxybenzotriazole monohydrate (HOBt.H2O, 69 mg, 0.45 mmole) and N-methylmorpholine (71 μL) were stirred in DMF (2 mL) for 20 minutes at room temperature prior to adding 2-amino-3-(6-bromo-2H-pyrazolo[4,3-b]pyridin-2-yl)-2-methylpropionitrile (100 mg, 0.357 mmole, described in Example 182). The mixture was stirred overnight at room temperature, quenched with a saturated solution of ammonium chloride and extracted with EA. The organic layer was washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a residue that was purified by chromatography (SiO2, heptane/EA) to afford the title compound as a white solid (17 mg, 9%). MS (ES): M/Z [M+H]=486. 1H NMR: (400 MHz, CHLOROFORM-d): 1.91 (s, 3H), 4.90 (d, J=14.1 Hz, 1H), 5.08 (d, J=14.1 Hz, 1H), 7.07 (d, J=12.1 Hz, 1H), 7.17 (d, J=8.4 Hz, 1H), 8.02 (d, J=12.1 Hz, 1H), 8.15-8.28 (m, 2H), 8.38 (s, 1H) and 8.62 (d, J=2.0 Hz, 1H). 19F NMR (376 MHz, CHLOROFORM-d): −108.6 (td, J=11.9, 9.2 Hz, 1F) and −58.3 (s, 3F). 2-fluoro-4-trifluoromethoxybenzoic acid was prepared as follows:

Provenance & Evidence