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Boc-beta-methoxyalanine dicyclohexylamine (80 mg, 0.2 mmol) was dissolved in DMF (4 mL). The solution was cooled to 0 C. and dipyrrolidino(N-succinimidyloxy)carbenium hexafluorophosphate (90.5 mg, 0.22 mmol) was added in one portion. 30 muL triethylamine was added and mixture was stirred at 0 C. for 15 minutes. A solution of amine (TFA.H-4F-Phe-naphth) (87.3 mg, 0.2 mmol) in 1 mL DMF and 30 muL Et3N was added to the reaction mixture. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was diluted with chloroform and washed with 1N HCl, water, aq. NaHCO3, water and brine. The organic layer was evaporated and purified by column chromatography to give product with traces of urea (dipyrrolidin-1-ylmethanone) byproduct. The crude was used in next step without further purification. 1H NMR (500 MHz, DMSO-d6) delta 8.46 (t, J=5.6 Hz, 1H), 8.07 (d, J=8.3 Hz, 1H), 8.02-8.00 (m, 1H), 7.96-7.94 (m, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.56-7.53 (m, 2H), 7.43 (dd, J=8.2, 7.0 Hz, 1H), 7.30 (d, J=6.9 Hz, 1H), 7.22-7.19 (m, 2H), 7.04-6.99 (m, 2H), 6.88 (d, J=8.1 Hz, 1H), 4.72 (d, J=5.6 Hz, 2H), 4.61-4.54 (m, 1H), 4.14-4.10 (m, 1H), 3.35 (d, J=6.1 Hz, 2H), 3.15 (s, 3H), 3.00 (dd, J=13.8, 5.4 Hz, 1H), 2.84 (d, J=13.8, 8.8 Hz, 1H), 1.45-1.30 (m, 9H). |