97845-60-8

Basic information

• Product Name: 9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine
• Synonyms: 9-(4-ACETOXY-3-ACETOXYMETHYLBUT-1-YL)-2-AMINO-6-CHLOROPURINE;9-[4-Acetoxy-3-(acetoxymethyl)butyl]-2-amino-6-chl;9-(4-ACETOXY-3-ACETOXYMETHYLBUT-1-YL)-2-AMINO-6-CHLOROPUINE;9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine;1,3-Propanediol,2-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]diacetate(ester)(9Cl;9-(4-Acetoxy-3-aceto;2-(2-(2-AMino-6-chloro-9H-purin-9-yl)ethyl)propane-1,3-diyl diacetate;9-(4-ACETOXY-3)-ACETOXYMETHYLBURYL-2-AMINO-6-CHLOROPURINE
• CAS NO: 97845-60-8
• Molecular Formula: C₁₄H₁₈ClN₅O₄
• Molecular Weight: 355.78
• EINECS: 1308068-626-2
• Product Categories: API intermediates
• Mol File: 97845-60-8.mol
• Article Data: 13

Chemical Properties

• Melting Point: 132-134 °C(Solv: isopropanol (67-63-0))
• Boiling Point: 574.979 °C at 760 mmHg
• Flash Point: 301.536 °C
• Appearance: /
• Density: 1.496 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.64
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.23±0.10(Predicted)
• CAS DataBase Reference: 9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine(CAS DataBase Reference)
• NIST Chemistry Reference: 9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine(97845-60-8)
• EPA Substance Registry System: 9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine(97845-60-8)

Safety Data

• Hazardous Substances Data: 97845-60-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine is used as an impurity in the production of Famciclovir, an antiviral agent. Famciclovir is a prodrug of Penciclovir, which is used to treat various viral infections, including herpes simplex and varicella-zoster virus infections. The presence of this impurity may affect the efficacy and safety of the antiviral treatment.

InChI:InChI=1/C14H18ClN5O4/c1-8(21)23-5-10(6-24-9(2)22)3-4-20-7-17-11-12(15)18-14(16)19-13(11)20/h7,10H,3-6H2,1-2H3,(H2,16,18,19)

Upstream product

• 108-24-7 acetic anhydride 
• 172529-94-1 2-amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine 
• 128139-38-8 Acetic acid 2-acetoxymethyl-4-methanesulfonyloxy-butyl ester 
• 10310-21-1 2-Amino-6-chloropurin 
• 97845-72-2 2-[(acetyloxy)methyl]-4-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)butyl acetate 
• 17495-10-2 N²-acetyl-7-benzylguanine 
• 118-00-3 G 
• 6979-94-8 2',3',5'-tri-O-acetyl-guanosine 
• 256945-18-3 N²-acetyl-9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]guanine 
• 55387-85-4 3-hydroxymethyl-4-hydroxybutanal diethyl acetal 
• 21339-47-9 diethyl 2-(2,2-diethoxyethyl)malonate 
• 333335-46-9 (5-ethoxy-tetrahydro-furan-3-yl)-methanol 
• 333335-48-1 benzoic acid 5-hydroxy-tetrahydro-furan-3-ylmethyl ester 
• 333335-47-0 benzoic acid 5-ethoxy-tetrahydro-furan-3-ylmethyl ester 

Downstream Products

• 104227-87-4 9-(4-acetoxy-3-acetoxymethylbutyl)-2-aminopurine 
• 39809-25-1 Penciclovir 
• 172529-94-1 2-amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine 
• 104227-86-3 6-deoxypenciclovir 
• 120687-07-2 (R,S)-9-<4-acetoxy-3-(hydroxymethyl)but-1-yl>-2-aminopurine 
• 120687-10-7 (R,S)-2-amino-9-<4-(benzyloxy)-3-(hydroxymethyl)but-1-yl>purine 
• 115932-75-7 9-<4-hydroxy-3-(hydroxymethyl)but-1-yl>-2-<(monomethoxytrityl)amino>purine 
• 120711-22-0 (R,S)-9-<3-(hydroxymethyl)-4-<(monomethoxytrityl)oxy>but-1-yl>-2-<(monomethoxytrityl)amino>purine 

Relevant articles and documents

Preparation method of penciclovir

The invention discloses a preparation method of penciclovir. An existing synthetic route mainly has the following defects that the N-7 site by-products need to be removed through column chromatography, a large amount of three wastes are generated, and the yield of N-9 site products is not high. According to the technical scheme adopted by the invention, the preparation method comprises the following steps: carrying out alkylation on 2-amino-6-chloropurine and triethyl bromopropane under an alkaline condition to introduce an N-9 site side chain, carrying out decarboxylation and transesterification in a methanol solution of sodium methoxide to generate the 2-amino-6-chloro-9-(3,3-dimethoxycarbonyl-1-propyl)purine; then reducing the 2-amino-6-chloro-9-(3,3-dimethoxycarbonyl-1-propyl)purine togenerate 2-amino-6-chloro-9-(3-hydroxymethyl-4-hydroxy-1-butyl)purine with sodium borohydride; and finally, directly hydrolyzing under acidic conditions to obtain penciclovir. According to the method, the target product is obtained by directly hydrolyzing the reduction product, ester group protection and deprotection are not needed, and the method has the advantages of few reaction steps, good product quality, simplicity and convenience in operation, suitability for industrial production and the like.

Preparation method for 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine

The invention relates to a preparation method for 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine. The method comprises the following steps: performing a reaction on 1,3-dichloro-2-propanoland an acetate to obtain 1,3-diacetoxy-2-propanol, performing a bromination reaction to obtain 1,3-diacetoxy-2-bromopropane, performing a reaction on the 1,3-diacetoxy-2-bromopropane and zinc powder to obtain 1,3-diacetoxy-2-zinc bromide propane, performing a coupling reaction on the 1,3-diacetoxy-2-zinc bromide propane and 2-bromoethanol protected by hydroxyl, and performing a de-protection reaction to obtain 1,3-diacetoxy-2-(2-hydroxyethyl)propane, and performing a Mitsunobu reaction on the 1,3-diacetoxy-2-(2-hydroxyethyl)propane and 2-amino-6-chloropurine to obtain the 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine. According to the method provided by the invention, the 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine prepared by the method has purity of 99.5% or more detected by HPLC, and can be used to prepare famciclovir and penciclovir.

Method for preparing 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine

The invention relates to a method for preparing 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine. The method comprises the following steps: reacting 1,3-dichloro-2-propanol with acetic acid to obtain 1,3-diacetoxy-2-propanol, brominating the 1,3-diacetoxy-2-propanol to obtain 1,3-diacetoxy-2-bromopropane, and reacting the 1,3-diacetoxy-2-bromopropane with zinc powder to obtain 1,3-diacetoxy-2-propylzinc bromide, and then performing a Negishi Coupling reaction on the 1,3-diacetoxy-2-propylzinc bromide and chloro-9-bromoethylpurine to obtain 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine. The obtained 2-amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine has an HPLC purity of 99.5% or more, and can be used for producing famciclovir and penciclovir.

Virtual Screening of Acyclovir Derivatives as Potential Antiviral Agents: Design, Synthesis, and Biological Evaluation of New Acyclic Nucleoside ProTides

Following our findings on the anti-human immunodeficiency virus (HIV) activity of acyclovir (ACV) phosphate prodrugs, we herein report the ProTide approach applied to a series of acyclic nucleosides aimed at the identification of novel and selective antiv

A process for the manufacture of famciclovir using phase-transfer catalysts

The invention relates to a process for the preparation of Famciclovir, which comprises the preparation of a compound of formula (II) wherein X is a halogen atom by reaction of a compound of formula (III) with a compound of formula (VII) wherein L is a leaving group, in the presence of a catalytic amount of a quaternary ammonium salt, followed by hydrogenation of compound (II) to Famciclovir.

Practical syntheses of penciclovir and famciclovir from N2-acetyl-7-benzylguanine

We have established practical methods for the synthesis of penciclovir (PCV) and famciclovir (FCV) from readily available guanosine via N2-acetyl-7-benzylguanine. The alkylation of N2-acetyl-7-benzylguanine proceeded selectively at the N9 position to give the desired alkylated product in good yield in salt form. After conventional catalytic hydrogenolysis of the benzyl group and hydrolysis of the resulting acetate, pure PCV was obtained without the need for chromatography. As a side chain precursor, the mesylate was selected rather than a halide since the corresponding halides gave several impurities under the same reaction conditions. Two procedures for the synthesis of FCV from PCV and a derivative are also reported.

A PROCESS FOR THE PREPARATION OF 2-ACETOXYMETHYL-4 HALO-BUT-1-YL ACETATES

A process for the preparation of 2- acetoxymethyl-4-halo-but-l-yl acetates (I) in which X is chlorine or bromine, which are useful intermediates for the preparation of antiviral medicaments such as Penciclovir and Famciclovir, comprising the opening of 3-hydroxymethyl-tetrahydrofuran (V) in the presence of an acylating agent and a Lewis acid selected from magnesium bromide and samarium triiodide.

Production method of famciclovir and production and crystallization method of intermediate therefor

An N-9-position alkylated form is selectively precipitated by subjecting a mixture containing the N-9-position alkylated form and an N-7-position alkylated form of 2-amino-6-halopurine to a crystallization step using a mixed solvent of an organic solvent and water. Then, this N-9-position alkylated form is reduced to give famciclovir. By this method of the present invention, famciclovir known as an antiviral agent, and an intermediate compound therefor can be efficiently produced.

Regioselective alkylation of guanines using 2-acetoxytetrahydrofurans

Reaction of silylated guanine derivatives with 2-acetoxy-4-benzoyloxymethyltetrahydrofuran in DMF or NMP resulted in selective N-9 alkylation. This was used as the basis for a regioselective synthesis of the anti-viral agents famciclovir and penciclovir.

Convenient syntheses of 9-[4-hydroxy-3-(hydroxymethyl)butyl]guanine (penciclovir) and 9-[4-acetoxy-3-(acetoxymethyl)butyl]-2-amino-9h-purine (famciclovir)

Guanine 11 was converted, in a one pot reaction, into 2-amino-6-[(4- chlorophenyl)sulfanyl]purine 9a in 88% isolated yield. 4-Acetoxy-3- (acetoxymethyl)butanol 123 was prepared from 2-chloroethanol in five steps and in 46% overall yield. The mesylate ester of compound 23 reacted with 9a in the presence of potassium carbonate with a high degree of regioselectivity (89%) to give the N-9 alkylated product 26 which was isolated in 80% yield. Acidic hydrolysis of the latter compound 26 gave penciclovir 4 in virtually quantitative yield. Penciclovir 4 and famciclovir 5 were prepared from 2- amino-6-[(4-chlorophenyl)sulfanyl]purine 9a in four and five steps, respectively, by procedures involving initial alkylation with 1,2- dibromoethane. The overall yields obtained were 65 and ca. 60%, respectively.