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Aminoacid acidamide compounds and preparation thereof

A technology for amino acid amides and amine compounds, which is applied in the preparation of carboxylic acid amides, the preparation of organic compounds, chemical instruments and methods, etc. It can solve the problems of low reaction efficiency and stable protective groups, and achieve simple reaction methods and post-processing Easy and efficient effect

Inactive Publication Date: 2008-12-24
GUANGZHOU CHEM CO LTD CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the protecting groups BOC and CBZ cannot exist stably under strong acidic conditions, and the protected amino acids cannot form acid chlorides; while the amino acids protected by the protecting group Fmoc can form acid chlorides, but when they react with simple amines in a homogeneous system, they will be removed. protection, so that the reaction efficiency is very low. If the reaction with amines can be realized directly, it will overcome the constraints that BOC and CBZ need to be deprotected under strong acid or palladium-carbon reduction systems. The protection group Fmoc can be removed in a simple Quick and gentle removal in the presence of amine compounds (piperidine, methylamine, etc.), simple method, high efficiency, easy post-treatment

Method used

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  • Aminoacid acidamide compounds and preparation thereof
  • Aminoacid acidamide compounds and preparation thereof
  • Aminoacid acidamide compounds and preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] (1) Synthesis of N-Fmoc-L-valyl chloride

[0032] Dissolve 15.0g N-Fmoc-L-valine (44.2mmol) in 250ml CH 2 Cl 2 , pass into N 2 For protection, add 32.1ml SOCl dropwise 2 (442.0mmol), heated to 50°C, refluxed for 4 hours, then changed to a distillation device, and evaporated most of the CH 2 Cl 2 Afterwards, it was evaporated to dryness under reduced pressure and dried under vacuum at 60° C. for 2 h to obtain 15.5 g of N-Fmoc-L-valyl chloride as a light yellow solid with a yield of 98%.

[0033] (2) Synthesis of N-Fmoc-N'-methyl-L-valinamide

[0034] Dissolve 15.5 g (44.2 mmol) of the above solid product into 465 g of anhydrous ether, and quickly add 26.0 g of an aqueous solution of 25% to 30% methylamine (221.0 mmol) 5 times the molar weight of the above solid product after dissolution, and shake vigorously for 3 minutes , suction filtration, the solid was washed in 800ml of water, suction filtration, and then washed with 800ml of water, suction filtration, repeat...

Embodiment 2

[0038] (1) Synthesis of N-Fmoc-L-valyl chloride

[0039]Dissolve 15.0g N-Fmoc-L-valine (44.2mmol) in 250ml CH 2 Cl 2 , pass into N 2 For protection, add 32.1ml SOCl dropwise 2 (442.0mmol), heated to 50°C, refluxed for 4 hours, then changed to a distillation device, and evaporated most of the CH 2 Cl 2 Afterwards, it was evaporated to dryness under reduced pressure and dried under vacuum at 60° C. for 2 h to obtain 15.5 g of N-Fmoc-L-valyl chloride as a light yellow solid with a yield of 98%.

[0040] (2) Synthesis of N-Fmoc-N'-isopropyl-L-valinamide

[0041] 15.5 g (44.2 mmol) of the above-mentioned solid product was dissolved in 310 g of anhydrous toluene. After the dissolution was complete, 10.1 g of isopropylamine (176.8 mmol) solution of 4 times the molar weight of the above-mentioned solid product was quickly added, vigorously shaken for 4 minutes, suction filtered, and The solid was washed in 600ml of water, filtered with suction, and then washed with 600ml of wate...

Embodiment 3

[0045] (1) Synthesis of N-Fmoc-L-leucyl chloride

[0046] Dissolve 10.0g N-Fmoc-L-leucine (28.3mmol) in 75ml CH 2 Cl 2 , pass into N 2 For protection, add 20.6ml SOCl dropwise 2 (283.0mmol), heated to 50°C, and refluxed for 2 hours, then changed to a distillation device, and evaporated most of the CH 2 Cl 2 Afterwards, it was evaporated to dryness under reduced pressure and dried under vacuum at 60° C. for 2 h to obtain 10.3 g of N-Fmoc-L-leucyl chloride as a light yellow solid with a yield of 98%.

[0047] (2) Synthesis of N-Fmoc-N'-methyl-L-leucineamide

[0048] Dissolve 10.0 g (26.9 mmol) of the above solid product into 400 g of anhydrous toluene. After the dissolution is complete, quickly add 9.5 g of an aqueous methylamine solution (80.7 mmol) 3 times the molar weight of the above solid product, shake vigorously for 2 min, and filter with suction. The solid was washed in 600ml of water, filtered with suction, washed with 600ml of water again, filtered with suction, ...

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Abstract

The invention discloses an amino acid amide compound and a preparation method thereof. Amino acid protected by FMOC and an acyl chloride reagent react to produce amino acid acyl chloride which is dissolved into a solvent with an appropriate polarity and reacts with a simple compound with primary amine and secondary amine so that the prepared amino acid amide compound can precipitate once forming in the reaction process, thereby reducing the contact of the FMOC and the amine; the whole process is short in the reaction time and fast in speed, thereby preventing the de-protection and realizing that the amino acid protected by the FMOC reacts with the simple amine on the premise without removing protective group; and the yield is up to more than 93 percent. The reaction method is simple, and has high efficiency and clean products as well as easy post treatment.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to an amino acid amide compound and a preparation method thereof. Background technique [0002] Amino acid amide compounds are a very important class of pharmaceutical intermediates and synthetic reagents, from which a variety of compounds with bactericidal and anti-tumor activities, enhanced immunity and fatigue resistance of biological organisms can be derived and synthesized, and are important for the synthesis of complex functional proteins. Raw materials are also important carriers for selective adsorption of chiral compounds, and have been widely concerned in the fields of chemistry, biology, and medicine. [0003] At present, there are two main methods for synthesizing amino acid amides: one is to convert amino acid carboxyl groups into more active groups that are more conducive to ammonolysis, such as esters, acid anhydrides, etc., and then ammonolysis; Preparation by dehyd...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C237/06C07C237/02C07C231/02C07C323/58C07C319/20C07D207/16
CPCY02P20/55
Inventor 胡继文刘志雷孙建平胡美龙
Owner GUANGZHOU CHEM CO LTD CHINESE ACADEMY OF SCI
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