2-hydrazino adenosine and preparation method thereof

A technology of hydrazinoadenosine and hydrazinoadenosine dihydrate, which is applied in the field of medicine and can solve the problems of cumbersome preparation and purification, high cost, and low yield

Inactive Publication Date: 2017-08-18
南京海辰药业股份有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Moreover, only 2-hydrazinoadenosine has been obtained in the description of the prior art, and 2-hydrazinoadenosine dihydrate has not been obtained
The preparation and purification of 2-halo (fluoro, chloro, iodo) adenosines are cumbersome, with low yield and high cost

Method used

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  • 2-hydrazino adenosine and preparation method thereof
  • 2-hydrazino adenosine and preparation method thereof
  • 2-hydrazino adenosine and preparation method thereof

Examples

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preparation example Construction

[0026] In the method for preparing 2-hydrazinoadenosine dihydrate 1 of the present invention, the amount of hydrazine hydrate is 0.5 to 10 times, preferably 1 to 2 times, the volume of the compound of formula II.

[0027] In the preparation method of the present invention, the reaction solvent may be one or more mixtures of water, methanol, ethanol, n-propanol or isopropanol. Among them, water, methanol or ethanol may be used as a preferable reaction solvent, and methanol is particularly preferable. The amount of the reaction solvent used is 1-10 times, preferably 1-5 times, particularly preferably 2-3 times the volume of the compound of formula II.

[0028] In the preparation method of the present invention, the reaction temperature is 0-100°C, preferably 50-90°C, particularly preferably 80-90°C.

[0029] In the preparation method of the present invention, the reaction time is 1-10 hours, preferably 2-8 hours, particularly preferably 5-7 hours.

[0030] A crystalline form o...

Embodiment 1

[0037] Example 1: Synthesis of 2-hydrazinoadenosine dihydrate

[0038]

[0039] Add 50g of 2',3',5'-triacetyl-2-chloroadenosine (IIa) into 100mL of hydrazine hydrate, and react at a temperature of 80-90°C for 5h. Cool down to 10-20°C and stir for 1h. Filter, wash with water and ethanol, suck dry, and dry under reduced pressure at 50°C for 6 hours to obtain 31.9 g of off-white solid. Yield 81.9%. Moisture 10.9%, purity (HPLC) 97.4%.

Embodiment 2

[0040] Example 2: Synthesis of 2-hydrazinoadenosine dihydrate

[0041] Add 50g of 2',3',5'-triacetyl-2-chloroadenosine (IIa) into 50mL of hydrazine hydrate and 100mL of ethanol, and react at a temperature of 80-90°C for 5h. Cool down to 10-20°C and stir for 1h. Filter, wash with ethanol, suck dry, and dry under reduced pressure at 50°C for 6 hours to obtain 36.8 g of off-white solid. Yield 94.5%. Moisture 10.8%, purity (HPLC) 98.5%.

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Abstract

The invention belongs to the field of pharmaceutical chemical engineering and relates to 2-hydrazino adenosine and a preparation method thereof. According to the method disclosed by the invention, a chemical compound shown as a formula II reacts with hydrazine hydrate in the presence or the absence of a polar solvent and the reaction formula is shown as follows. The 2-hydrazino adenosine crystal prepared by adopting the method is high in yield, high in purity and low in cost; the method has the advantages of being friendly to the environment, simple and convenient to operate and easy in industrial scale-up and has a very good industrial application prospect; and the 2-hydrazino adenosine can be used for preparing an adenosine receptor agonist, i.e. regadenoson.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a new crystal form of 2-hydrazinoadenosine, a key intermediate of an adenosine receptor agonist Regadenoson, and a preparation method thereof. Background technique [0002] 2-hydrazinoadenosine is a key intermediate in the synthesis of adenosine receptor agonist Regadenoson. [0003] [0004] Regadeson is a selective A drug jointly developed by American CV Pharmaceuticals and Astellas. 2a Adenosine receptor agonists, which have been marketed in the United States and Europe, are mainly used as coronary vasodilators for myocardial perfusion imaging. Prior art (WO00 / 78779, WO2007092372, US7183264, Journal of Medicinal Chemistry, 35 (24), 4557-61) methods for preparing 2-hydrazinoadenosine are all 2-halo (fluorine, chlorine, iodine) substituted adenosine Prepared by reacting with hydrazine hydrate. Moreover, only 2-hydrazinoadenosine was obtained in the description...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H19/167C07H1/00
CPCY02P20/55C07H19/167C07B2200/13C07H1/00
Inventor 冯明声周丽君罗艳滕红菊姚晓敏曹于平
Owner 南京海辰药业股份有限公司
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