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With pyridine; thionyl chloride In dichloromethane Heating; |
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With thionyl chloride In dichloromethane |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; |
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With thionyl chloride In dichloromethane at 20℃; for 24h; |
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With oxalyl dichloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; |
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With thionyl chloride In toluene for 2h; Heating; |
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With thionyl chloride |
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With thionyl chloride In dichloromethane for 1h; Heating; |
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With thionyl chloride In dichloromethane for 0.5h; Sonication; |
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With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 2h; Reflux; |
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With thionyl chloride In dichloromethane at 20℃; for 0.5h; |
4.2.3. Synthesis of compound 2
Compound 3 (1.687 g, 5 mmol) was dissolved in CH2Cl2 (20 mL) and mixed with dripping SOCl2 (1 mL, 3 equiv). The mixture was stirred at room temperature for 30 min and decompressed at 40 °C to remove HCl formed during the reaction, as well as the solvent and superfluous SOCl2, generating a yellow oil product. Into the yellow oil were added NH4SCN (0.570 g, 7.5 mmol), polyethylene glycol (PEG)-400 (0.053 mL, 0.15 mmol) and CH2Cl2 (25 mL) at room temperature within 1 h to give isothiocyanate. A certain amount of resin 4 was then added to the mixture with isothiocyanate and stirred at room temperature. After being stirred for 24 h, water was added to dissolve the salt formed during the reaction, and ethanol was used to precipitate the product. Compound 2, either a yellow or light yellow solid, was obtained after filtering, and then washing with water, CH2Cl2 and acetone, and drying in a vacuum. |
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With 2,4,6-trimethyl-pyridine; bis(trichloromethyl) carbonate In tetrahydrofuran |
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With thionyl chloride for 5h; Reflux; |
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With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h; |
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With thionyl chloride In dichloromethane at 20℃; Sonication; Inert atmosphere; |
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With thionyl chloride In dichloromethane |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; |
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With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 23℃; for 2h; Inert atmosphere; |
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With thionyl chloride In dichloromethane at 37℃; for 1.75h; |
Synthesis of functionalized monomer 3
Fmoc-L-Pro (1.49g, 4.42mmol) was dissolved with CH2Cl2 (3mL) in a flask. To the resultant solution was slowly added 1mL of SOCl2 at 37°C with 15min of stirring. The mixture was stirred at 37°C for 1.5h to afford acyl chloride 2. Next, p-aminostyrene was dissolved in pyridine and added to acyl chloride 2 in 30min while the temperature was kept under 25°C for 6h. The resultant N-Fmoc was deprotected prior to polymerization with diethylamine with stirring overnight to give the functionalized monomer 3 |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; Inert atmosphere; |
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With thionyl chloride In dichloromethane at 20℃; Inert atmosphere; Sonication; |
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With 2,4,6-trimethyl-pyridine; bis(trichloromethyl) carbonate In tetrahydrofuran for 0.166667h; Inert atmosphere; |
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With thionyl chloride In dichloromethane for 3h; Reflux; |
10 Synthesis of Fmoc-L-Proline Acid Chloride
Fmoc-L-proline (250 mg, 0.74 mmol) was dissolved in CH2Cl2 (4 mL). Thionyl chloride (800 μL, 10.36 mmol) was added and the solution was stirred at reflux for 3 h with monitoring by quenching with methanol as a diluent and following the formation of the methanol adduct by TLC (CH2Cl2:MeOH; 9:1). Subsequently the reaction was dried in vacuo to give 250 mg of crude, which was then used in the subsequent reaction without any further purification. |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; |
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With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; |
9.1 Functionalization of Aza-peptide with native amino acid:
[00303] 1. Preparation of the Fmoc-Pro(Cl): To a solution of Fmoc-Proline (1.0 g, 3.0 mmol) in DCM (lOmL) was added 0.1 mL of DMF. At 0°C, the reaction mixture was treated with thionyl chloride (2.0 mL). The reaction mixture was brought gradually to room temperature and left stirring for an additional 2h. The volatiles was removed under vacuum, and the residue was triturated with a solution of ether: hexane (1 : 1, v/v) (10 mL). The residue was dried under high vacuum for 30 min and used in the next step without further treatment. |
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With thionyl chloride In dichloromethane Sonication; |
2.1. Brief Procedure for the Preparation of AminoacylChloride
General procedure: In a 50 mL round bottomed flask, N-Fmoc-protectedamino acid (1mmol), dichloromethane (CH2Cl2) 6 mL andfreshly distilled thionyl chloride (1.2 mmol) was added andthe mixture was sonicated till the reaction completion, thereaction was monitored by TLC. After reaction, the excessof thionyl chloride and DCM were removed under vacuum,followed by addition of hexane separates solid product, itwas filtered and dried under vacuum taken directly for thereaction for the reaction [49]. |