Z-gln-大苏

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a mixed liquid of 100 ml of acetic acid, 100 ml of 25% HBR-acetic acid and 3.4 g of anisole is dissolved 33.5 g (30.9 millimoles) of Z-Arg(Tos)-Leu-Leu-Gln-Gly-Leu-Val-NH2, and the solution is stirred at room temperature for 1.5 hours and is then added to 2.5 l of ether. The formed precipitate is recovered by decantation and dissolved in 300 ml of ethanol. The solution is added to ether and an HBr salt of the Z-compound is recovered by decantation. Then, the recovered salt (34.5 g, 30.9 millimoles) is dissolved in 400 ml of dimethylformamide, and 6.8 g of N-methylmorpholine is added to the solution under cooling. Then, 14 g (37 millimoles) of crystalline Z-Gln-OSu is added to the mixture, and the mixture is stirred at -5° C. for 2 hours and allowed to stand at room temperature for 2 days. Then, 2 g of N-(2-aminoethylpiperazine) is added to the reaction mixture, and the mixture is stirred for 30 minutes and added to 2.5 l of 1 N HCl. The formed precipitate is recovered by filtration, washed with water, suspended in 400 ml of methanol, stirred and recovered by filtration to obtain 31.5 g of intended Z-Gln-Arg(Tos)-Leu-Leu-Gln-Gly-Leu-Val-NH2 (the yield being 84.2%). The formed precipitate is recovered by decantation dissolved in 300 ml of ethanol The solution is added to ether an HBr salt of the Z-compound is recovered by decantation under cooling the mixture is stirred at -5° C. for 2 hours to stand at room temperature for 2 days the mixture is stirred for 30 minutes The formed precipitate is recovered by filtration washed with water stirred recovered by filtration

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-((2,2-Dimethyl-4-oxo-3,8,11,14,17,20,23,26,29,32, 35,38-dodecaoxa-5-azatetracontan-40-yl)carbamoyl)-2-undecyltridecanedioic acid (20 mg, 0.018 mmol) in THF (Volume: 2 mL) was added to Z-L-Gln-Osu (Santa Cruz Biotechnology, CAS 34078-85-8, 11 mg, 0.029 mmol), then DIPEA (75 μl, 0.429 mmol) was added. Stirred at room temperature under a nitrogen atmosphere over weekend. Complete conversion was observed by LCMS (Acidic Eluent A: Water+0.05% Trifluoroacetic Acid, Eluent B: ACN, column Sunfire C18 3.5 μm 3.0×30 mm −40° C., 5-95% gradient 2 minutes, retention time 1.77 min) The reaction mixture was concentrated under reduced pressure and then dissolved in acetonitrile. Purified on a MS-triggered HPLC (Sunfire 30×50 mm Sum column ACN/H2O w/0.1% TFA 75 ml/min 1.5 ml injection, 55-80% ACN 3.5 min gradient, retention time 2.70 minutes) and the fractions pooled and lyophilized to give 10.5 mg clean product ZQ-FA in 46% yield as a clear colorless oil. was concentrated under reduced pressure dissolved in acetonitrile Purified on a MS-triggered HPLC (Sunfire 30×50 mm Sum column ACN/H2O w/0.1% TFA 75 ml/min 1.5 ml injection, 55-80% ACN 3.5 min gradient, retention time 2.70 minutes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a mixed liquid of 100 ml of acetic acid, 100 ml of 25% HBR-acetic acid and 3.4 g of anisole is dissolved 33.5 g (30.9 millimoles) of Z-Arg(Tos)-Leu-Leu-Gln-Gly-Leu-Val-NH2, and the solution is stirred at room temperature for 1.5 hours and is then added to 2.5 l of ether. The formed precipitate is recovered by decantation and dissolved in 300 ml of ethanol. The solution is added to ether and an HBr salt of the Z-compound is recovered by decantation. Then, the recovered salt (34.5 g, 30.9 millimoles) is dissolved in 400 ml of dimethylformamide, and 6.8 g of N-methylmorpholine is added to the solution under cooling. Then, 14 g (37 millimoles) of crystalline Z-Gln-OSu is added to the mixture, and the mixture is stirred at -5° C. for 2 hours and allowed to stand at room temperature for 2 days. Then, 2 g of N-(2-aminoethylpiperazine) is added to the reaction mixture, and the mixture is stirred for 30 minutes and added to 2.5 l of 1 N HCl. The formed precipitate is recovered by filtration, washed with water, suspended in 400 ml of methanol, stirred and recovered by filtration to obtain 31.5 g of intended Z-Gln-Arg(Tos)-Leu-Leu-Gln-Gly-Leu-Val-NH2 (the yield being 84.2%). The formed precipitate is recovered by decantation dissolved in 300 ml of ethanol The solution is added to ether an HBr salt of the Z-compound is recovered by decantation under cooling the mixture is stirred at -5° C. for 2 hours to stand at room temperature for 2 days the mixture is stirred for 30 minutes The formed precipitate is recovered by filtration washed with water stirred recovered by filtration