Hydrochloric Acid → HCID 76286518, compound

Participants

Reaction Steps

To a solution of the product from Example 1, Part D (50 mg, 0.134 mmol) in anhydrous methanol (2 mL) was added 4 M HCl in 1,4-dioxane (0.334 mL, 1.335 mmol), and the resulting mixture was stirred at room temperature for 18 hours and concentrated in vacuo. The residue was dissolved in a mixture of dichloromethane (8 mL) and triethylamine (0.093 mL, 0.668 mmol), and then 5-(trifluoromethyl)picolinic acid (0.026 g, 0.134 mmol), 1-hydroxybenzotriazole hydrate (0.025 g, 0.160 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.031 g, 0.160 mmol) were added. The resulting mixture was stirred at room temperature for 16 hours, and then it was partitioned between water and ethyl acetate. The organic extract was washed successively with water and brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-4% methanol in dichloromethane to give the title compound as a waxy solid (0.042 g, 70%). 1H NMR (400 MHz, pyridine-d5) δ ppm 9.05-8.97 (m, 1H), 8.28-8.13 (m, 2H), 8.11 (dd, J=19.6, 1.4 Hz, 1H), 8.00 (dd, J=18.4, 8.2 Hz, 1H), 5.45-5.32 (m, 1H), 4.59 (dd, J=13.5, 2.2 Hz, 1H), 4.14-3.95 (m, 1H), 3.85-3.68 (m, 1H), 3.59 (dd, J=12.1, 6.0 Hz, 2H), 3.18 (ddd, J=17.4, 13.7, 9.8 Hz, 1H), 3.10-2.94 (m, 2H), 2.64-2.53 (m, 1H), 2.51-2.38 (m, 1H), 2.16-1.70 (m, 4H), 1.14-0.98 (m, 2H), 0.99-0.84 (m, 2H); MS (ESI) m/z 448 (M+H)+.

Provenance & Evidence