Hydrochloric Acid → HCID 86680530, compound

Participants

Reaction Steps

To a solution of the product from Example 54F and (5)-2-(tert-butoxy-carbonyl(methyl)amino)-4-methylpentanoic acid (51.8 mg, 0.211 mmol) in anhydrous N,N-dimethylformamide (2.5 mL) was added 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (110 mg, 0.288 mmol) and 4-methylmorpholine (0.042 mL, 0.384 mmol). The resulting mixture was stirred at room temperature for 90 minutes and then was partitioned between water and ethyl acetate (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in a mixture of 1,4-dioxane (1 mL) and hydrogen chloride (4 N in 1,4-dioxane, 1 mL, 4.00 mmol), and the resulting mixture was stirred at room temperature for 2 hours and then concentrated in vacuo. The residue was partitioned between saturated aqueous NaHCO3 solution and dichloromethane (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane. The title compound was obtained as a colorless solid (53 mg, 71%). 1H NMR (300 MHz, CDCl3) δ ppm 0.87-1.03 (m, 10 H), 1.23-1.52 (m, 2 H), 1.76-2.06 (m, 4 H), 2.17-2.49 (m, 6.5 H), 2.74-2.96 (m, 1 H), 2.98-3.10 (m, 1 H), 3.12-3.26 (m, 0.5 H), 3.36-3.52 (m, 1 H), 3.73 (dd, J=9.83, 6.78 Hz, 1 H), 3.88 (d, J=13.22 Hz, 0.5 H), 4.00 (d, J=12.55 Hz, 0.5 H), 4.66 (d, J=13.56 Hz, 0.5 H), 4.81 (d, J=11.87 Hz, 0.5 H), 5.31-5.42 (m, 1 H), 7.92-7.97 (m, 1 H), 8.00-8.06 (m, J=7.80 Hz, 1 H); MS (ESI) m/z 388 (M+H)+.

Provenance & Evidence