CN112876524A

CN112876524A - Preparation method of Reidesciclovir intermediate

Info

Publication number: CN112876524A
Application number: CN202110103155.8A
Authority: CN
Inventors: 唐家邓; 王小梅; 茆勇军; 张诗伟; 余志明
Original assignee: Shanghai Famo Biotechnology Co ltd
Current assignee: Shanghai Famo Biotechnology Co ltd
Priority date: 2021-01-26
Filing date: 2021-01-26
Publication date: 2021-06-01
Anticipated expiration: 2041-01-26
Also published as: CN112876524B

Abstract

The invention discloses a preparation method of a Reidesciclovir intermediate, which comprises the steps of firstly reacting 7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-amine with N, N-dimethylformamide dimethyl acetal, then adding i-PrMgCl or butyl lithium into the product obtained in the previous step for reaction, then adding 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone, and finally removing a protecting group to obtain the Reidesciclovir intermediate 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (benzyl) -D-ribofuranose. According to the preparation method of the Ruidexilvir intermediate, the product which is mature in the current market is selected as the reactant, the raw materials are easy to obtain, and the production cost is reduced; the method has the advantages of simple process, short time consumption, high production efficiency, high yield, mild reaction conditions, simple and convenient post-treatment, suitability for amplified preparation and wide application prospect.

Description

Preparation method of Reidesciclovir intermediate

Technical Field

The invention belongs to the technical field of organic synthesis and preparation of raw material medicines, relates to a preparation method of a medical intermediate, and particularly relates to a novel preparation method of an intermediate of an antiviral drug Rudexilvir.

Background

Reddeevir (Remdesivir) is a drug developed by Gilidd science, a nucleoside analogue with antiviral activity, and has an EC50 value of 74nM for SARS-CoV and MERS-CoV in HAE cells and an EC50 value of 30nM for murine hepatitis virus in delayed brain tumor cells. Reidesvir has a broad spectrum antiviral activity that has been shown to be effective against a variety of emerging viral pathogens in vitro and in vivo studies in animal models, including Ebola virus, Marburg virus, Middle East Respiratory Syndrome (MERS), and atypical pneumonia (SARS) virus. The antiviral drug Reidevir approved by the United states Food and Drug Administration (FDA) for Jilide science is used for treating Xinguan inpatients in 22/10/2020, and becomes the first officially approved Xinguan therapeutic drug in the United states.

In the chemical synthesis of the Reidesciclovir, the key intermediate 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (benzyl) -D-ribofuranose (A) is most difficult to synthesize, and the chemical structure is shown as the following formula:

with respect to the synthesis of compound a, two main types of methods are now reported:

the synthetic route is shown in formula I (WO2012012776, WO2014035140, WO2015069939, US20160122374, CN 111793101, CN 111620876, Nature 531,381-385,2016, J.Med.chem.,60,1648-1661,2017, Org.Process Res.Dev.,24, 1772-171777 and 2020). The method takes 7-bromopyrrolo [2,1-f ] [1,2,4] triazine-4-amine (B) or 7-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-amine (C) as a raw material, and the raw material reacts with 2,3, 5-tribenzyloxy-D-ribono-1, 4-lactone (D) under different conditions to obtain A. The bromide B is used as a raw material, TMSCl is used for protecting amino, n-butyl lithium is used as alkali for reaction, and the yield is about 20-40% (the method a and the method B). The iodo compound C is used as a raw material, TMSCl is used for protecting amino, and a Grignard reagent is used as an alkali for reaction, so that the yield is increased to 40-69% (method C and method d). However, because the property of the benzyloxyribose (D) is active, the benzyloxyribose (D) is easily destroyed and decomposed by strong alkali, and if the qualified product A is obtained by the methods, column chromatography purification is usually needed, so that the production and application of the product are limited to a certain extent.

The second method (CN 109748921; CN 111187269) is improved on the basis of the first method, and the synthetic route is shown as a formula II. The preparation method comprises the steps of adopting a protecting group introducing mode to prepare a BOC protected pyrrolotriazine-4-amine compound (E, F, G), reacting with benzyloxyribose (D) under different conditions, and removing the BOC to obtain A. LDA or n-butyllithium is used as alkali, the yield fluctuation of different substrates is large, reported methods are laboratory small-scale methods, and products need to be purified by column chromatography and are not suitable for large-scale preparation.

Therefore, there is a need to improve the prior art to overcome the defects in the prior art, and to provide a preparation method with easily available raw materials, simple process, convenient operation and higher yield.

Disclosure of Invention

The invention aims to overcome the defects that the existing preparation method is difficult to amplify and prepare and has low production efficiency, and provides a method for preparing a Rudexilvir intermediate (specifically 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazine-7-yl) -2,3, 5-trioxa- (benzyl) -D-ribofuranose) with easily obtained raw materials, simple process, convenient operation and higher yield.

In order to achieve the purpose, the invention provides the following technical scheme:

a preparation method of a Reidesciclovir intermediate, wherein the Reidesciclovir intermediate is 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazine-7-yl) -2,3, 5-trioxo- (benzyl) -D-ribofuranose, and the structural formula is as follows:

the preparation route of the Ruideciclovir intermediate is shown as the following formula:

firstly, 7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-amine (compound C in the above formula) is reacted with N, N-dimethylformamide dimethyl acetal (DMF-DMA) to generate N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (i.e. compound H in the above formula);

then, I-PrMgCl or butyl lithium is added into the product N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide in the previous step for reaction, then 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone (namely the compound D in the formula) is added to generate the compound I in the formula, and finally, the protecting group is removed to prepare the Reidesvir intermediate 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (benzyl) -D-ribofuranose (namely the compound A in the formula).

According to the preparation method of the Ruidexiwei intermediate, the product-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-amine which is mature in the current market is selected as a reactant, so that the production cost can be obviously reduced, the yield of an acetal reaction is high (up to 91%), the post-treatment is convenient, the three wastes are few, in addition, the whole process is simple, the whole time consumption is short, the time consumption of the subsequent treatment process is short, the process is simple and convenient to operate, meanwhile, the yield can reach 60-70%, compared with the prior art, the yield is greatly improved, the reaction time is greatly shortened, and meanwhile, the preparation method is suitable for large-scale preparation and has a great application prospect.

As a preferred technical scheme:

the preparation method of the Rudexilvir intermediate has the advantage that in the step (1), the reaction temperature is 70-100 ℃.

In the preparation method of the Rudexilvir intermediate, in the step (2), the reaction temperature of the reaction with i-PrMgCl or butyl lithium and the reaction with 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone is the same or different, and is-70 ℃ to-20 ℃.

In the preparation method of the ridciclovir intermediate, in the step (2), recrystallization purification is carried out on the product after the protective group is removed.

In the above method for preparing a ridciclovir intermediate, in the step (2), the deprotection is performed by adding an aqueous ammonium chloride solution to the reaction solution. The protection scope of the present invention is not limited to the above limitations, and only one feasible technical solution is given here, and one skilled in the art can adjust the reaction temperature at each stage according to actual needs and select appropriate technical means to remove the protecting group.

Has the advantages that:

(1) according to the preparation method of the Rudexilvir intermediate, a mature product in the current market, namely the iodopyrrolo [2,1-f ] [1,2,4] triazin-4-amine, is selected as a reactant, raw materials are easy to obtain, and the production cost can be obviously reduced;

(2) the preparation method of the Ruidexilvir intermediate has the advantages of simple overall process, short overall time consumption, high production efficiency, high yield, mild reaction conditions, simple and convenient post-treatment, suitability for scale-up preparation and great application prospect.

Detailed Description

The present invention will be described in more detail with reference to the following embodiments, which are illustrative only of some embodiments of the invention and not all embodiments of the invention.

Example 1

A preparation method of a Ruidesacvir intermediate 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazine-7-yl) -2,3, 5-trioxo- (benzyl) -D-ribofuranose comprises the following steps:

(1) preparation of N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (i.e., Compound H, hereinafter referred to as H):

adding 7-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-amine (26.0g, 0.1mol) into a 500mL three-necked bottle, adding 260mL of ethanol, then adding N, N-dimethylformamide dimethyl acetal (DMF-DMA) (13.1g, 0.11mol), heating to 70-80 ℃ for reacting for 2H to generate a solid suspension, cooling the reaction solution to room temperature, stirring in an ice water bath for 1H, carrying out suction filtration on the generated solid, washing a filter cake with ethanol (15mL multiplied by 2 times), and drying at 50 ℃ for 8H to obtain light yellow solid powder H (28.0g, 91%);

(2) preparation of 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (phenylmethyl) -D-ribofuranose (i.e., Compound A, hereinafter referred to as A):

taking N' - (7-iodopyrrolo [2, 1-f)][1,2,4]Triazin-4-yl) -N, N-dimethylformamide (H) (15.7g, 0.05mol) was charged into a 500mL three-necked flask, 120mL of anhydrous tetrahydrofuran was added, nitrogen was substituted 3 times, and the mixture was cooled to-20 to-30 ℃. 1.3M i-PrMgCl was added dropwise thereto^.LiCl complex in tetrahydrofuran (58mL, 0.075mol) was controlled at-20-30 ℃ for 30 min. 2,3, 5-Tribenzyloxy-D-ribono-1, 4-lactone (D) (23.0g, 0.055mol) is dissolved in 40mL of anhydrous tetrahydrofuran, and the solution is dripped into the reaction solution and reacted at-20 to-30 ℃ for 30 min. 20mL of a saturated aqueous ammonium chloride solution was added dropwise to the reaction mixture, followed by addition of 200mL of water, and the mixture was stirred at room temperature for 30 min. Adding 300mL of ethyl acetate, stirring, standing, and separating. The organic layer was washed with water (300 mL. times.1). The organic phase was concentrated to dryness under reduced pressure to give 29g of a light brown foamy solid. Adding 15mL of isopropyl acetate into the solid, stirring and dissolving at 60 ℃, adding 100mL of methyl tert-butyl ether, stirring at 0-10 ℃ for 4 hours, and gradually precipitating the solid. The filter cake was washed with suction, tert-butyl methyl ether (10 mL. times.2) and dried at 40 ℃ for 6h to give white solid A (19.6g, 71%).

The nuclear magnetic resonance spectrum of the compound H prepared in the step (1) is as follows:

¹H NMR(400MHz,DMSO-d₆):δ3.16(s,3H),3.22(s,3H),6.93(dd,J＝13.6,4.4Hz,2H),8.15(s,1H),8.92(s,1H)；

¹³C NMR(100MHz,DMSO-d₆):δ35.4,41.5,72.0,105.3,120.2,124.2,148.6,158.7,160.1；

HRMS(ESI)calcd for:C₉H₁₁IN₅[M+H]⁺316.00591,Found:316.00540.

the nuclear magnetic resonance spectrum of the compound A prepared in the step (2) is as follows:

H-NMR(400MHz,DMSO-d₆):δ8.06(brs,2H),7.99(s,1H),7.37-7.22(m,11H),7.19-7.10(m,3H),7.03-6.97(m,2H),6.95(d,J＝4.8Hz,1H),5.39(d,J＝5.9Hz,1H),5.05(d,J＝5.2Hz,1H),4.61-4.54(m,2H),4.52-4.42(m,4H),4.06-3.98(m,1H),3.93(dd,J＝5.9,4.4Hz,1H),3.69(dd,J＝10.1,3.4Hz,1H),3.47(dd,J＝10.0,6.4Hz,1H)；

¹³C-NMR(100MHz,DMSO-d₆):δ187.98,155.88,148.96,138.63,138.43,138.14,128.67,128.14,128.12,127.82,127.54,127.44,127.26,127.21,127.09,118.60,117.51,103.15,102.30,81.91,80.92,72.50,72.33,71.74,71.44,69.42；

ESI-MS(m/z)553.3[M+H]⁺.

high Performance Liquid Chromatography (HPLC) test results:

HPLC: column: InertSustain C18(250 mm. times.4.6 mm. times.5 μm); detection wavelength: 210nm, 244 nm; flow rate: 0.8 mL/min; column temperature: 30 ℃; sample introduction amount: 1 mu L of the solution; solvent: MeOH; concentration: 0.2 mg/mL; operating time: 30 min; mobile phase A: water; mobile phase B: methanol/formic acid 100/0.1; and (3) elution: mobile phase a/mobile phase B10/90; t is t_R9.175min, purity: 99.9% (210nm), 98.2% (244 nm).

Example 2

adding 7-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-amine (26.0g, 0.1mol) into a 250mL three-necked bottle, adding 100mL DMF, then adding N, N-dimethylformamide dimethyl acetal (DMF-DMA) (13.1g, 0.11mol), heating to 90-100 ℃ for reaction for 0.5H, cooling the reaction solution to room temperature, evaporating the solvent under reduced pressure to obtain a brown oily substance, adding 250mL ethanol into the oily substance, stirring for 1H in an ice water bath, separating out a solid, performing suction filtration, washing a filter cake with ethanol (5mL multiplied by 2 times), and drying for 8H at 50 ℃ to obtain a light yellow solid H (25.2g, 81%);

adding N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (H) (15.7g, 0.05mol) into a 250mL three-necked bottle, adding 120mL of anhydrous tetrahydrofuran, replacing 3 times with nitrogen, cooling to-20-30 ℃, dropwise adding a 2M i-PrMgCl tetrahydrofuran solution (38mL, 0.075mol) into the three-necked bottle, and reacting at-20-30 ℃ for 30min for later use;

adding 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone (D) (23.0g, 0.055mol) into a 500mL three-necked bottle, adding 80mL of anhydrous tetrahydrofuran, replacing 3 times with nitrogen, and cooling to-20-30 ℃;

transferring the standby solution to a constant-pressure dropping funnel, dropwise adding the solution into a 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone (D) tetrahydrofuran solution, controlling the temperature to be between-20 and-30 ℃ for reaction for 30min, dropwise adding 50mL of saturated ammonium chloride aqueous solution into the reaction solution, heating to room temperature, concentrating the solvent under reduced pressure to obtain brown paste, adding 300mL of ethyl acetate and 200mL of water, stirring, standing, separating, washing the organic layer with water (200mL multiplied by 2 times), and concentrating and drying the organic layer under reduced pressure to obtain 27g of light brown foamy solid;

the product was purified by column chromatography to give 13.3g of pale yellow foamy solid A, 48% yield, 94% high performance liquid purity.

Preparation of Compound H from step (1)¹H NMR、¹³Results of C NMR and HRMS (ESI) and of Compound A obtained in step (2)¹H NMR、¹³The results of C NMR and HRMS (ESI) and HPLC analysis were the same as in example 1.

Example 3

adding 7-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-amine (26.0g, 0.1mol) into a 250mL three-necked bottle, adding N, N-dimethylformamide dimethyl acetal (DMF-DMA) (60g, 0.50mol), heating to 90-100 ℃ for reaction for 0.5H, cooling the reaction liquid to room temperature, distilling off the solvent under reduced pressure to obtain a brown oily substance, adding 150mL of methanol into the oily substance, stirring in an ice-water bath for 1H, separating out a solid, performing suction filtration, washing a filter cake with methanol (5mL multiplied by 2 times), and drying at 50 ℃ for 8H to obtain a light yellow solid H (21.1g, 67%);

adding N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (H) (15.7g, 0.05mol) into a 500mL three-necked bottle, adding 120mL of anhydrous tetrahydrofuran, replacing with nitrogen for 3 times, and cooling to-60 to-70 ℃; dropwise adding 2.5M n-BuLi (namely butyl lithium) tetrahydrofuran solution (30mL, 0.075mol) into the mixture, and controlling the temperature to be-60 to-70 ℃ for reaction for 30 min; dissolving 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone (D) (23.0g, 0.055mol) in 40mL of anhydrous tetrahydrofuran, dropwise adding into the reaction solution, and reacting at-60 to-70 ℃ for 30 min; 30mL of a saturated aqueous ammonium chloride solution was added dropwise to the reaction mixture, 200mL of water was added thereto, and the mixture was stirred at room temperature for 30 min. Adding 300mL of ethyl acetate, stirring, standing and separating liquid; the organic layer was washed with water (300 mL. times.1); decompressing and concentrating the organic phase to obtain 31g of light brown foamy solid; adding 15mL of isopropyl acetate into the solid, stirring and dissolving at 60 ℃, adding 100mL of methyl tert-butyl ether, stirring at 0-10 ℃ for 4h, and then dropwise adding 20mL of n-heptane to gradually separate out the solid; performing suction filtration, washing a filter cake (10mL multiplied by 2 times) by methyl tert-butyl ether, and drying at 40 ℃ for 6h to obtain a white soft solid A (14.1g, 51%); the purity of the high-efficiency liquid phase is 92 percent.

Preparation of Compound H from step (1)¹H NMR、¹³C NMR and HRMS (ESI) chart and preparation of Compound A from step (2)¹H NMR、¹³The C NMR, HRMS (ESI) and HPLC detection results are the same as in example 1.

Example 4

(1) preparation of N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (i.e., Compound H, hereinafter referred to as H) was the same as described in example 1;

adding N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (H) (15.7g, 0.05mol) into a 500mL three-necked bottle, adding 120mL of anhydrous tetrahydrofuran, replacing with nitrogen for 3 times, and cooling to-20-25 ℃; dropwise adding a 2M i-PrMgCl tetrahydrofuran solution (38mL, 0.075mol) into the mixture, and controlling the mixture to react for 30min at the temperature of between 20 ℃ below zero and 25 ℃ below zero; dissolving 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone (D) (23.0g, 0.055mol) in 40mL of anhydrous tetrahydrofuran, dropwise adding into the reaction solution, and reacting at-20 to-25 ℃ for 30 min; 50mL of a saturated aqueous ammonium chloride solution was added dropwise to the reaction mixture, and 200mL of water was added thereto, followed by stirring at room temperature for 30 min. Concentrating the solvent under reduced pressure to obtain a light brown paste; to this mixture were added 200mL of ethyl acetate and 100mL of water, and the mixture was stirred at room temperature for 30min, allowed to stand, and separated. The organic layer was washed with brine (100mLx1 times). Decompressing and concentrating the organic phase to obtain light brown foamy solid 30 g; adding 15mL of isopropyl acetate into the solid, stirring and dissolving at 60 ℃, adding 100mL of methyl tert-butyl ether, stirring at 0-10 ℃ for 4h, and dropwise adding 15mL of n-heptane to gradually separate out the solid. Performing suction filtration, washing a filter cake (10mL multiplied by 2 times) by methyl tert-butyl ether, and drying at 40 ℃ for 6h to obtain a white solid A (18.8g, 68%); the purity of the high-efficiency liquid phase is 97 percent.

Example 5

(2) preparation of 1-C- (4-Aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (phenylmethyl) -D-ribofuranose (i.e., Compound A, hereinafter referred to as A) is the same as described in example 2.

Example 6

(2) preparation of 1-C- (4-Aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (phenylmethyl) -D-ribofuranose (i.e., Compound A, hereinafter referred to as A) is the same as described in example 3.

Example 7

(1) preparation of N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (i.e., Compound H, hereinafter referred to as H) was the same as described in example 2;

(2) preparation of 1-C- (4-Aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (phenylmethyl) -D-ribofuranose (i.e., Compound A, hereinafter referred to as A) is the same as described in example 1.

Example 8

Example 9

(2) preparation of 1-C- (4-Aminopyrrole [2,1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxo- (phenylmethyl) -D-ribofuranose (i.e., Compound A, hereinafter referred to as A) is the same as described in example 4.

Example 10

(1) preparation of N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide (i.e., Compound H, hereinafter referred to as H) was the same as described in example 3;

Example 11

Example 12

Proved by verification, the preparation method of the Rudexilvir intermediate selects the mature product-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-amine in the current market as a reactant, has easily obtained raw materials, and can obviously reduce the production cost; the whole process is simple, the whole time consumption is short, the production efficiency is high, the yield is high, the reaction condition is mild, the post-treatment is simple and convenient, and the method is suitable for large-scale preparation and has a great application prospect.

Although specific embodiments of the present invention have been described above, it will be appreciated by those skilled in the art that these embodiments are merely illustrative and various changes or modifications may be made without departing from the principles and spirit of the invention.

Claims

1. A preparation method of a Reidesciclovir intermediate, wherein the Reidesciclovir intermediate is 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazine-7-yl) -2,3, 5-trioxo- (benzyl) -D-ribofuranose, is characterized in that 7-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-amine and N, N-dimethylformamide dimethyl acetal react, i-PrMgCl or butyl lithium react is added into the product obtained in the previous step, 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone is added, and finally a protecting group is removed to prepare the Reidesciclovir intermediate 1-C- (4-aminopyrrole [2 ], 1-f ] [1,2,4] triazin-7-yl) -2,3, 5-trioxa- (benzyl) -D-ribofuranose.

2. A process for preparing a ridciclovir intermediate according to claim 1, comprising the steps of:

(1) reacting 7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-amine with N, N-dimethylformamide dimethyl acetal to produce N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-yl) -N, N-dimethylformamide;

(2) adding i-PrMgCl or butyl lithium into N' - (7-iodopyrrolo [2,1-f ] [1,2,4] triazine-4-yl) -N, N-dimethylformamide for reaction, then adding 2,3, 5-tribenzyloxy-D-ribonic acid-1, 4-lactone for reaction, and finally removing a protecting group to prepare the Reidesciclovir intermediate 1-C- (4-aminopyrrole [2,1-f ] [1,2,4] triazine-7-yl) -2,3, 5-trioxo- (benzyl) -D-ribofuranose.

3. A preparation method of a Reidesciclovir intermediate according to claim 2, wherein the reaction temperature in step (1) is 70-100 ℃.

4. A process for preparing a ridciclovir intermediate according to claim 2, wherein in step (2), the reaction temperature for the reaction with i-PrMgCl or butyllithium and the reaction with 2,3, 5-tribenzyloxy-D-ribono-1, 4-lactone is the same or different from-70 ℃ to-20 ℃.

5. A process for preparing a ridciclovir intermediate according to claim 2, wherein in step (2), after removing the protecting group, the product is purified by recrystallization.

6. A process for preparing a ridciclovir intermediate according to claim 2, wherein in step (2), the deprotection is carried out by adding an aqueous solution of ammonium chloride to the reaction solution.