Diisopropylethylamine → tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamate

Participants

Reaction Steps

Pybop (164 mg, 0.32 mmol), diisopropylethylamine (50 mg, 0.39 mmol) and N-boc-L-valine (69 mg, 0.32 mmol) were added to a solution of N-(4-amino-5-methyl-3-oxohexyl)-2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamide (Cpd. No. 3, lot 2, 75 mg, 0.11 mmol) in methylene chloride (5 mL) at 0° C. The resulting mixture was stirred at room temperature for 5 h. The reaction mixture was then diluted with methylene chloride (15 mL) and washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by prep-scale reverse phase high performance liquid chromatography to provide tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamate (Cpd. No. 49,100 mg) as a white solid. 1H NMR (CDCl3): 8.86 (d, 1H), 7.98 (s, 1H), 7.45-7.33 (m, 5H), 5.98 (s, 1H), 5.66 (br s, 1H), 4.98 (br s, 1H), 4.55-4.51 (m, 2H), 4.11-4.02 (m, 3H), 3.00-2.93 (m, 2H), 2.20 (m, 1H), 1.48 (s, 9H), 1.09 (d, 3H), 0.90 ppm (d, 3H).

Provenance & Evidence