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Synthesis method of (4R,5R)-4,5-bi (aminomethyl)-1,3-bioxyamyl cyclic kind compound

A dioxolane and aminomethyl technology, applied in the -4 field, can solve the problems of low total yield, long reaction steps and high cost, and achieve the effects of convenient operation, low cost and simple process route

Inactive Publication Date: 2007-02-14
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to overcome the existing problems in the prior art such as longer reaction steps, lower total yield, use of toxic raw materials and higher cost, and proposes an environmentally friendly, simple process and low cost ( 4R, 5R)-4,5-bis(aminomethyl)-1,3-dioxolane compound synthesis preparation method

Method used

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  • Synthesis method of (4R,5R)-4,5-bi (aminomethyl)-1,3-bioxyamyl cyclic kind compound
  • Synthesis method of (4R,5R)-4,5-bi (aminomethyl)-1,3-bioxyamyl cyclic kind compound
  • Synthesis method of (4R,5R)-4,5-bi (aminomethyl)-1,3-bioxyamyl cyclic kind compound

Examples

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Embodiment 1

[0026] Example 1: Synthesis of (4R, 5R)-4,5-bis(aminomethyl)-2-ethyl-1,3-dioxolane: taking D-dimethyl tartrate as starting material, followed by Prepared through the following steps:

[0027] (1) Acetalization, that is, the synthesis of 2,3-oxygen-propylene-D-dimethyl tartrate:

[0028] 17.8g of D-dimethyl tartrate, 8.7g of propionaldehyde, 100ml of anhydrous toluene, 4g of anhydrous copper sulfate, stirred and reacted at 60°C for 4h. Stop heating, cool to room temperature, separate the organic layer, wash with 5% sodium bicarbonate until neutral, then wash with saturated brine, wash with water, and spin off the solvent to obtain 2,3-oxo-propylene-D-tartaric acid Diethyl ester 16.7g, yield 76.7%.

[0029] (2) Ammonolysis, that is, the synthesis of (4R, 5R)-4,5-bis(formamide)-2-ethyl-1,3-dioxolane:

[0030] Put 21.8g of the above-mentioned 2,3-oxy-propylene-D-tartrate dimethyl ester into a 100m1 three-neck bottle, add 30ml of concentrated ammonia water, stir and react at 70°...

Embodiment 2

[0033] Example 2: Synthesis of (4R, 5R)-4,5-bis(aminomethyl)-2-ethyl-1,3-dioxolane: taking D-dimethyl tartrate as starting material, followed by Prepared through the following steps:

[0034] (1) Acetalization, that is, the synthesis of 2,3-oxygen-propylene-D-dimethyl tartrate:

[0035] 17.8g of D-dimethyl tartrate, 8.7g of propionaldehyde, 100ml of anhydrous toluene, and 3.0g of phosphorus pentoxide were stirred and reacted at 20°C for 20h. The organic layer was separated, washed with 5% sodium bicarbonate until neutral, then washed with saturated brine, washed with water, and the solvent was rotated to obtain 9.5 g of 2,3-oxo-propylene-D-diethyl tartrate. Rate 43.5%.

[0036] (2) Ammonolysis, that is, the synthesis of (4R, 5R)-4,5-bis(formamide)-2-ethyl-1,3-dioxolane:

[0037] Put 21.8g of the above-mentioned 2,3-oxy-propylene-D-tartrate dimethyl ester into a 100ml three-necked bottle, add 30ml of concentrated ammonia water, stir and react at 50°C, and gradually solids ar...

Embodiment 3

[0040] Example 3: Synthesis of (4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane: starting with D-diethyl tartrate, Prepared through the following steps:

[0041] (1) Acetalization, that is, the synthesis of 2,3-oxo-isobutylene-D-diethyl tartrate:

[0042] 20.6g of D-diethyl tartrate, 14.4g of isobutyraldehyde, 100ml of anhydrous toluene, and 3.0g of phosphorus pentoxide were placed in a 500ml three-necked bottle, and stirred and reacted at 100°C for 3h. Cool to room temperature, separate the organic layer, wash with 5% sodium bicarbonate until neutral, then wash with saturated brine, wash with water, and spin off the solvent to obtain 2,3-oxo-isobutylene-D-diethyl tartrate 23.7 g of ester, yield 91.3%.

[0043] (2) Ammonolysis, that is, the synthesis of (4R, 5R)-4,5-bis(formamide)-2-isopropyl-1,3-dioxolane:

[0044] Put 26.0g of 2,3-oxo-isobutylidene-D-diethyl tartrate into a 100ml three-necked bottle, add 50ml of concentrated ammonia water, and react at 100°C. Solid...

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Abstract

The present invention relates to one kind of diamine compound synthesizing process, and is especially preparation process of (4R, 5R)-4, 5-bis(aminomethyl)-1, 3-dioxolane compounds. The present invention prepares (4R, 5R)-4, 5-bis(aminomethyl)-1, 3-dioxolane compounds with D-tartaric diester as the initial material and through successive acetlation or ketalation, ammonolysis and reductin. The synthesis process of the present invention has environment friendship, simple technological process, low cost, and average total yield of 61.2 %.

Description

Technical field: [0001] The invention relates to a synthesis method of diamine compounds, in particular to a preparation method of (4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane compounds. Background technique: [0002] [0003] Wherein R is an aliphatic alkyl group with 1 to 8 carbon atoms, or an aromatic hydrocarbon group with 6 to 9 carbon atoms. Especially when R is isopropyl, I is (4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane, which is a synthetic antineoplastic drug heptaplatin important intermediates. Existing technology adopts following method to prepare: [0004] Dae-Kee Kim et al. (J.Med.Chem, 1994,37,1471; J.LabelledCompd.Radiopharm, 1994,34,157; ​​J.Am.Chem.Soc, 1978,100,4865) reported that D-tartaric acid The diester is used as a raw material, which is synthesized in five steps. This method not only has long steps, but also uses highly toxic and explosive sodium azide, and the total yield is also low, so it is harmful to human body and environment an...

Claims

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Application Information

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IPC IPC(8): C07D317/28
Inventor 王德才江建欧阳平凯潘勇赵敏
Owner NANJING UNIV OF TECH