* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
(S)-4-benzyl 1-tert-butyl 2-(4-(5-((((R)-2-((R)-1-(N-(benzyloxy)formamido)propyl)heptanamido)methyl)carbamoyl)furan-2-yl)-2-ethoxybenzamido)succinate[ No CAS ]
(S)-4-benzyl 1-tert-butyl 2-(4-bromo-2-ethoxybenzamido)succinate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 1.0h;
Step 1 : (S)-4-benzyl 1-tert-butyl 2-(4-bromo-2-ethoxybenzamido)succinate DIPEA (7.48 ml_, 42.8 mmol) was added to a stirring solution containing 4-bromo-2- ethoxybenzoic acid (3.5 g, 14.28 mmol),(S)-4-(benzyloxy)-1-(tert-butoxy)-1 ,4-dioxobutan-2- aminium chloride (4.96 g, 15.71 mmol), and HATU (6.52 g, 17.14 mmol) in DMF (40 ml_). The resulting solution was stirred at RT for 1 h. Water was added followed by EtOAc. The organics were washed with brine (2x). The combined washes were back-extracted using EtOAc. The combined organics were dried over MgS04, filtered, and concentrated. Purification by Si (0-100% EtOAc/Hex) afforded the title compound as a colorless oil. (7.03 g, 100% yield). MS (m/z) 506.0 (M+H)+
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 4.0h;
[0456] To a solution of 0.250 g (1.50 mmol) of 3-(3-hydroxyphenyl)propanoic acid in DMF (7 mL) was added 0.500 g (1.58 mmol) of 4-benzyl l-(tert-butyl) L-aspartate hydrochloride followed by 0.65 g (1.7 mmol) of HATU and 0.90 mL (5.2 mmol) of DIEA. The mixture was stirred at room temperature for 4 hours then diluted with water and extracted with EtOAc. The combined organic phase was washed with IN HC1 followed by saturated aqueous sodium bicarbonate and brine. The mixture was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography and the eluent was concentrated under reduced pressure to provide 3-18-3 (0.587 g, 91%) as a clear oil.
With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 16.0h;
[0582] To a solution of 04-benzyl 01 -tert-butyl (2S)-2-aminobutanedioate (25 g, 79mmol, HC1 salt) and 5-hexenoic acid (10 g, 91 mmol) in DMF (500.00 mL) was added HATU (37 g, 99 mmol) at room temperature. After being stirred for 5 min, TEA (43.9 mL, 320 mmol) was added at room temperature and the mixture was stirred at room temperature for 16hours. Water was added and the mixture was extracted with EtOAc. The extract was washed with brine and water then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography to afford a residue (26.7 g, 89.8% yield) as a pale brown oil which was used as is. To the residue was added 2,2,2-trifluoroacetic acid (121.62 g, 1.07 mol) in an ice-bath, and the mixture was stirred at room temperature for 16 hours. Then the reaction mixture was concentrated under reduced pressure and azeotroped with toluene 3 times to afford, 4-10-1 (23 g, 102% yield) as a pale brown oil which was used for next step without further purifi cati on.