* 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.
(2-{2-[2-(2-{2-[2-(9<i>H</i>-fluoren-9-ylmethoxycarbonylamino)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethoxy)-acetic acid <i>tert</i>-butyl ester[ No CAS ]
With sodium hydrogencarbonate In tetrahydrofuran; 1,2-dimethoxyethane; water at 20℃; for 2h;
2 Preparation of Compound 6
Compound 5 (1.0 eq) was dissolved in 50 ml of purified water, 3.96 g of sodium bicarbonate (2.0 eq) was added, and 5.30 g of Fmoc-OSU (1.0 eq) was dissolved in 50 ml of DME and added to the reaction flask of compound 5. Add 25 ml of THF, stir at room temperature for 2 hours. After TLC monitoring is completed, evaporate the organic solvent, extract the impurities with EA, adjust the pH of the aqueous phase with dilute hydrochloric acid to 3-4, and extract the EA twice. Combine the organic phases, wash once, saturated brine. After washing with water, it was dried over anhydrous sodium sulfate and concentrated to give 8.4 g of compound 6 as a light yellow oil.
8.4 g
With sodium hydrogencarbonate In tetrahydrofuran; water; N,N-dimethyl-formamide at 20℃; for 2h;
2 Preparation of Compound 6
Compound 5 (1.0 eq) was dissolved in 50 mL of purified water, and 3.96 g of sodium bicarbonate (2.0 eq) was added. 5.30 g of Fmoc-OSU (1.0 eq) was dissolved in 50 mL of DMF, the mixture was added to the reaction flask containing Compound 5, 25 mL of THF was added additionally, and the mixture was stirred at room temperature for 2 hours. After the completion of the reaction was monitored by TLC, the organic solvent was removed by distillation, and EA was used to extract the impurities. The pH of the aqueous phase was adjusted to 3 to 4 with is dilute hydrochloric acid, the mixture was extracted twice with EA, and the organic phases were combined and washed once with water. After being washed with saturated saline, the mixture was dried over anhydrous sodium sulfate and concentrated to obtain 8.4 g of Compound 6 as a pale yellow oil.
With diethyl cyanophosphonate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;
In a 100 ml reaction flask, 4.00 g of compound 6 (1.0 eq), 2.92 g of H-Lys(Boc)-OBetazl·HCl was added Dissolve 40 ml of DCM, add 2.76 g of DIEA (3.0 eq), 1.74 g of DEPC (1.5 eq), and stir at room temperature for 2 hours. After TLC monitoring is completed, wash with acetic acid aqueous solution, wash with sodium bicarbonate solution, and wash once with water, and then wash once with saturated saline solution. Sodium sulphate was dried and concentrated to give 7.0 g of compound 7 as a pale yellow oil which was directly used in the next step without purification. (Using the same method to prepare compound 16)