Method for synthesizing 2-amino-6-methoxy-9-(beta-D-aralino)-9H-purine

Abstract

The invention discloses a new synthesis method for 2-amino-6-methoxy-9-(beta-D-arabinose glycosyl)-9H-purine which is a medicine for treating T cell lymphoblast leukemia or lymphoma. The method mainly comprises the following steps: after the acid catalyzed reaction of raw materials, forming a blocking group, carrying out the halogenating reaction in succession, then carrying out the quaternization, and carrying out the de-protecting reaction to generate an end product. The synthesis route has a simple and short route, moderate conditions, easy operation, low cost, high yield and easy amplification, and is suitable for the industrialized production.

Description

technical field [0001] The problem solved by the present invention is to provide a new method for the synthesis of 2-amino-6-methoxyl-9-(β-D-arabinosyl)-9H-purine, a medicine for treating T cell lymphoblastic leukemia or lymphoma . technical background [0002] 2-Amino-6-methoxy-9-(β-D-arabinosyl)-9H-purine, whose common name is nelarabine, is mainly used for the treatment of T cell lymphoblastic leukemia or lymphoma, currently There are mainly two synthetic methods reported in the literature: [0003] 1): Enzyme-catalyzed synthesis [0004] The route of enzymatic synthesis of 2-amino-6-methoxy-9-(β-D-arabinosyl)-9H-purine is shown in the figure below: [0005] [0006] The method has the advantages of short steps, stereospecificity, and no stereoisomers and isomers. The only patented method for 9H-purine (EP294114A2). The disadvantages of this method are: first, the two enzymes used in the synthesis process - purine nucleoside phosphorylase and uridine phosphorylase...

AI Technical Summary

Problems solved by technology

The disadvantages of this method are: first, the two enzymes used in the synthesis process - purine nucleoside phosphorylase and uridine phosphorylase (H) are very expensive and difficult to buy; second, the enzyme catalyzed reaction The time is long (J), need about 360 hours; Third, the enzymatic reaction needs a large amount of K 2 HPO4 and KH 2 PO4 buffer solution (I), thus requiring a large reaction apparatus

[0010] The main feature of this method is that the synthetic route is longer and the yield is lower, wherein the used deprotection reagent boron trichloride (K) is more expensive, and the deprotection step requires anhydrous anaerobic and -78 degree low temperature (L ), the reaction conditions are very harsh, the operation is cumbersome, and it is difficult to scale up production

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