WO2004007497A1 - Process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine - Google Patents

Process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine Download PDF

Info

Publication number
WO2004007497A1
WO2004007497A1 PCT/KR2003/001396 KR0301396W WO2004007497A1 WO 2004007497 A1 WO2004007497 A1 WO 2004007497A1 KR 0301396 W KR0301396 W KR 0301396W WO 2004007497 A1 WO2004007497 A1 WO 2004007497A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
acetoxymethyl
compound
aminopurine
acetoxy
Prior art date
Application number
PCT/KR2003/001396
Other languages
French (fr)
Inventor
Byoung-Suk Lee
Sang-Hoon Shin
Jong-Sik Park
Original Assignee
Kyungdong Pharm. Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kyungdong Pharm. Co., Ltd. filed Critical Kyungdong Pharm. Co., Ltd.
Priority to US10/521,352 priority Critical patent/US7041823B2/en
Priority to AT03741578T priority patent/ATE457987T1/en
Priority to AU2003281046A priority patent/AU2003281046B8/en
Priority to JP2004521270A priority patent/JP4231479B2/en
Priority to DE60331334T priority patent/DE60331334D1/en
Priority to EP03741578A priority patent/EP1551839B1/en
Publication of WO2004007497A1 publication Critical patent/WO2004007497A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • the present invention relates to a process for preparing 9- [4-acetoxy-3- (acetoxymethyl) ut-l-yl] -2- aminopurine (called Famciclovir) of Formula (I) , a drug of purine derivatives having antiviral activity:
  • the present invention relates to a novel process for preparing 9- [4-acetoxy-3 ⁇ (acetoxymethyl) ut-l-yl] -2-aminopurine (called
  • Famciclovir of Formula (I) , a drug of purine derivatives having antiviral activity, in which 2- aminopurine of Formula (II) is reacted with 2- acetoxymethyl-4-bromobut-l-yl-acetate of Formula (III) in the presence of thallium (I) ethoxide to give the compound of Formula (I) in high selectivity while minimizing the production of 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine of Formula (V), a reaction byproduct:
  • EP No. 182,024 and US Patent No. 5,684,153 discloses a process for preparing 9- [4 ⁇ acetoxy-3- (acetoxymethyl) but-l-yl] -2- aminopurine of Formula (I) , in which 2-amino- ⁇ - chloropurine of Formula (VI) is reacted with 2- acetoxymethyl-4-halobut-l-yl-acetate of Formula (VII) to give 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino-6- chloropurine of Formula (VIII) , which is then reduced into the compound of Formula (I) in the presence of palladium, as shown in Scheme 1 below.
  • Scheme 1 shows a process for preparing 9- [4 ⁇ acetoxy-3- (acetoxymethyl) but-l-yl] -2- aminopurine of Formula (I) , in which 2-amino- ⁇ - chloropurine of Formula (VI) is reacted with 2- acet
  • X is a halogen atom
  • US Patent No. 5,138,057 discloses a process for preparing 9- [4-acetoxy-3- (acetoxymethyl) but- l-yl] -2-aminopurine of Formula (I), in which 2-amino- 6, 8-dichloropurine of Formula (X) is reacted with 2- acetoxymethyl-4-halobut-l-yl-acetate of Formula (VII) to give 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino- 6, 8-dichloropurine of Formula (XI) which is then reduced under a pressurized condition in the presence of palladium, as shown in Scheme 3 below.
  • Scheme 3 shows a pressurized condition in the presence of palladium, as shown in Scheme 3 below.
  • US Patent No. 5,917,041 discloses a process for preparing 9- [4-acetoxy-3- (acetoxymethyl) but- l-yl] -2-aminourine of Formula (I), in which N-(2-amino- 4, 6-dichloro-5-pyrimidinyl) formamide of Formula (XIII) is reacted with 2-acetoxymethyl-4-aminobut-l-yl-acetate of Formula (XIV) to give a compound of Formula (XV) which is then converted into 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino-6-chloropurine of Formula (VIII) by means of triethylorthoformate of Formula (XVI) , and then the compound of Formula (VIII) is reduced into the compound of Formula (I) in the presence
  • Famciclovir 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] - 2-aminopurine
  • Famciclovir of Formula (I), a drug of purine derivatives having antiviral activity, can be prepared in a very high selectivity of 98% while minimizing the production of 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl-2- aminopurine of Formula (V) as a reaction byproduct
  • 2- aminopurin of Formula (II) is reacted with thallium (I) ethoxide of Formula (IV) in polar organic solvent at about 0-100 °C, and preferably about 10-30 °C, for about 2-50 hours, and preferably about 20-40 hours, to give 2- aminopurine-thallium salt of Formula (XXI) as an intermediate.
  • Famciclovir of Formula (I) is reacted with 2-acetoxy-4-bromobut-l-yl-acetate of Formula (III) in polar organic solvent at about 0-100 °C, and preferably about 10-30 °C, for about 50-200 hours, and preferably about 70-100 hours, to give Famciclovir of Formula (I) as the desired compound.
  • Famciclovir of Formula (I) and 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine of Formula (V) as a reaction product are produced at a ratio of 98%: 2%, the desired compound can be prepared in very high selectivity.
  • the compound of • Formula (II), which is used as the starting material in the process of the present invention, is commercially available or can be produced according to methods described in, for example, Heterocycles , 17, 405 (1982) and Journal of the Chemistry Society, 2060 (1954).
  • the compound of Formula (III), a branched hydrocarbon, which is used as the starting material in the process of the present invention can be prepared according to the conventional method, such a method described in European Patent Publication No. 141,927.
  • Preferred examples of the polar organic solvent which can be used in the preparing process of the present invention, include N, -dimethylformamide, dimethylsulfoxide, lower alcoholic solvents with 1-3 atoms, such as methanol, ethanol and isopropanol, and a mixture thereof.
  • IR vmax(cm _1 ) : 3330, 3160, 1743, 1728, 1645, 1606
  • Example 3 The solution was extracted three times with 70 ml of CHC1 3 , and dried over magnesium sulfate, and then concentrated under reduced pressure to evaporate the solvent. The residue was crystallized from a mixed solvent of ethyl acetate, hexane and tert-butanol, to give 8.35 g (52%) of 9- [4-acetoxy-3- (acetoxymethyl) but- l-yl] -2-aminopurine. Spectrum data analyzed for the compound obtained in Example 3 were identical to Example 2.
  • Famciclovir of Formula (I) , a drug of purine derivatives having antiviral activity, can be prepared in a very high selectivity under mild reaction conditions while minimizing the production of 7- [4- acetoxy-3- (acetoxymethyl) but-l-yl-2-aminopurine of Formula (V) as a reaction byproduct.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Disclosed is a process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine (called Famciclovir), a drug of purine derivatives having antiviral activity. This process comprises reacting 2-aminopurine with 2-acetoxymethyl-4-bromobut-1-yl-acetate in the presence of thallium (I) ethoxide to give the desired compound. According to this process, the desired compound can be prepared in very high selectivity and purity under mild reaction conditions.

Description

PROCESS FOR PREPARING 9- [4-ACETOXY-3- (ACETOXYMETHYL) BOT-l-Ϊ ] -2-AMINOPURINE
Technical Field
The present invention relates to a process for preparing 9- [4-acetoxy-3- (acetoxymethyl) ut-l-yl] -2- aminopurine (called Famciclovir) of Formula (I) , a drug of purine derivatives having antiviral activity:
Figure imgf000002_0001
More particularly, the present invention relates to a novel process for preparing 9- [4-acetoxy-3~ (acetoxymethyl) ut-l-yl] -2-aminopurine (called
Famciclovir) of Formula (I) , a drug of purine derivatives having antiviral activity, in which 2- aminopurine of Formula (II) is reacted with 2- acetoxymethyl-4-bromobut-l-yl-acetate of Formula (III) in the presence of thallium (I) ethoxide to give the compound of Formula (I) in high selectivity while minimizing the production of 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine of Formula (V), a reaction byproduct:
Figure imgf000003_0001
(0 <")
Figure imgf000003_0002
Background Art
Prior techniques for preparing the compound of Formula (I) are disclosed in European Patent No. 182,024, and US Patent Nos. 5,684,153, 5,138,057 and 5,917,041.
Among the above prior patents, EP No. 182,024 and US Patent No. 5,684,153 discloses a process for preparing 9- [4~acetoxy-3- (acetoxymethyl) but-l-yl] -2- aminopurine of Formula (I) , in which 2-amino-β- chloropurine of Formula (VI) is reacted with 2- acetoxymethyl-4-halobut-l-yl-acetate of Formula (VII) to give 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino-6- chloropurine of Formula (VIII) , which is then reduced into the compound of Formula (I) in the presence of palladium, as shown in Scheme 1 below. Scheme 1:
Figure imgf000004_0001
wherein X is a halogen atom.
However, the prior process according to Scheme 1 has problems in that the compound of Formula (VIII) and 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino-β- chloropurine of Formula (IX) as a byproduct are produced from the compound of Formula (VI) and the .compound of Formula (VII) at a ratio of 80%: 20%, as shown in Scheme 2 below, so that selectivity for the compound of Formula (VIII) is low and the purification of the compound of Formula (VIII) is very difficult. Scheme 2 :
Figure imgf000004_0002
80% : 20°/c 0
wherein X is a halogen atom. Furthermore, the process according to Scheme 1 above has problems in that it requires the use of highly explosive palladium in the preparation of the compound of Formula (I) as the desired compound from the compound of Formula (VIII) , and thus, is inefficient and unsuitable for industrial application.
Moreover, US Patent No. 5,138,057 discloses a process for preparing 9- [4-acetoxy-3- (acetoxymethyl) but- l-yl] -2-aminopurine of Formula (I), in which 2-amino- 6, 8-dichloropurine of Formula (X) is reacted with 2- acetoxymethyl-4-halobut-l-yl-acetate of Formula (VII) to give 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino- 6, 8-dichloropurine of Formula (XI) which is then reduced under a pressurized condition in the presence of palladium, as shown in Scheme 3 below. Scheme 3 :
Figure imgf000005_0001
Figure imgf000005_0002
However, the process according to Scheme 3 shows relatively high selectivity for the compound of Formula (XI), since the compound of Formula (XI) and 7- [4- acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino-6, 8- dichloropurine of Formula (XII) as a reaction byproduct are produced from the compound of Formula (X) and the compound of Formula (VII) at a ratio of 94%: 6%. However, this process has problems in that it requires the use of highly explosive palladium in the production of the compound of Formula (I) as the desired product from the compound of Formula (XI), as in EP No. 182,024 and US Patent No. 5,684,153, and needs to be carried out under a pressurized condition higher than 50 psi, thus posing difficulty in industrial application. In addition, US Patent No. 5,917,041 discloses a process for preparing 9- [4-acetoxy-3- (acetoxymethyl) but- l-yl] -2-aminourine of Formula (I), in which N-(2-amino- 4, 6-dichloro-5-pyrimidinyl) formamide of Formula (XIII) is reacted with 2-acetoxymethyl-4-aminobut-l-yl-acetate of Formula (XIV) to give a compound of Formula (XV) which is then converted into 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-amino-6-chloropurine of Formula (VIII) by means of triethylorthoformate of Formula (XVI) , and then the compound of Formula (VIII) is reduced into the compound of Formula (I) in the presence of palladium, as shown in Scheme 4 below.
Scheme 4
Figure imgf000007_0001
(0 (VIII)
However, the process according to Scheme 4 has problems in that it requires the use of expensive 2,5- diamino-4, 6-dihydroxypyrimidine of Formula (XVII) and expensive chloromethylene iminium salt of Formula
(XVIII) in the production of the compound of Formula
(XIII) as a starting material, as shown in Scheme 5 below, and gives the compound of Formula (I) as the desired product at a very low yield of about 32% via several steps from the compound of Formula (XVII) , and also requires the use of highly explosive palladium as in EP No. 182,024 and US Patent No. 5,684,153 as described above, so that it utilizes a long reaction route and is inefficient and thus has a difficulty in industrial application. Scheme 5:
Figure imgf000008_0001
Thus, in the relevant field of art, there has been demanded the development of a process which allows the preparation of 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] - 2-aminopurine (called Famciclovir) , a drug of purine derivatives having antiviral activity, at high selectivity under mild reaction conditions, while minimizing the production of 7- [4-acetoxy-3-
(acetoxymethyl) ut-l-yl] -2-aminopurine as a reaction byproduct.
Disclosure of the Invention
According to a preparing process of the present invention, owing to the introduction of thallium (I) ethoxide critical to this process, 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine (called
Famciclovir) of Formula (I), a drug of purine derivatives having antiviral activity, can be prepared in a very high selectivity of 98% while minimizing the production of 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl-2- aminopurine of Formula (V) as a reaction byproduct
Figure imgf000009_0001
More specifically, according to the process of the present invention as shown in Scheme 6 below, 2- aminopurin of Formula (II) is reacted with thallium (I) ethoxide of Formula (IV) in polar organic solvent at about 0-100 °C, and preferably about 10-30 °C, for about 2-50 hours, and preferably about 20-40 hours, to give 2- aminopurine-thallium salt of Formula (XXI) as an intermediate. Then, the compound of Formula (XXI) is reacted with 2-acetoxy-4-bromobut-l-yl-acetate of Formula (III) in polar organic solvent at about 0-100 °C, and preferably about 10-30 °C, for about 50-200 hours, and preferably about 70-100 hours, to give Famciclovir of Formula (I) as the desired compound. Moreover, according to the process of the present invention, since Famciclovir of Formula (I) and 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine of Formula (V) as a reaction product are produced at a ratio of 98%: 2%, the desired compound can be prepared in very high selectivity. Scheme 6:
Figure imgf000010_0001
The compound of • Formula (II), which is used as the starting material in the process of the present invention, is commercially available or can be produced according to methods described in, for example, Heterocycles , 17, 405 (1982) and Journal of the Chemistry Society, 2060 (1954). Also, the compound of Formula (III), a branched hydrocarbon, which is used as the starting material in the process of the present invention, can be prepared according to the conventional method, such a method described in European Patent Publication No. 141,927.
Preferred examples of the polar organic solvent, which can be used in the preparing process of the present invention, include N, -dimethylformamide, dimethylsulfoxide, lower alcoholic solvents with 1-3 atoms, such as methanol, ethanol and isopropanol, and a mixture thereof.
Best Mode for Carrying Out the Invention The present invention will hereinafter be described in further detail by examples. It should however be borne in mind that the present invention is not limited to or by the examples.
Example 1: Preparation of 2-aminopurine, thallium salt
6.75 g (50 mmole) of 2-aminopurine was suspended in 140 ml of anhydrous ethanol, and the temperature of a reactor was maintained below 15 °C. The suspension was added slowly with 18.72 g (75 mmole) of thallium (I) ethoxide, followed by stirring for 36 hours at room temperature. At the end of the reaction, the stirred mixture was filtered, and washed with anhydrous ethanol to give 15.57 g (92%) of 2-aminopurine-thallium salt. Melting point: 290-292 °C (dec.)
• IR: vmax (cm-1) : 3400, 3180, 3060, 2800, 1650, 1580, ■ 1512, 1421
1H NMR (DMSO-d6, 300MHz) (ppm) : 6.35 (2H, brs, -NH2) 8.13 (1H, s, H of C-8) 8.65 (1H, s, H of C-6)
Example 2__ Preparation of 9- [4-acetoxy-3-
(acetoxymethyl) but-l-yl] -2-aminopurine 16.92 g (50 mmole) of 2-aminopurine-thallium salt was suspended in 140 ml of N, N-dimethylformamide, and the temperature of a reactor was maintained below 15 °C . The suspension was added slowly with a solution of 16.03 g (60 mmole) of 2-acetoxymethyl-4-bromobut-l-yl-acetate in 30 ml of N, N-dimethylformamide, followed by stirring for 84 hours at room temperature. At the end of the reaction, the stirred mixture was cooled and filtered, and then the filtrate was concentrated under reduced pressure to evaporate the solvent. The residue was purified by silica gel chromatography (CHC13 :MeOH=90 : 1) to give 9.80 ■ g (61%) of 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine (Rf=0.82) . Melting point: 101-103 °C (dec.)
IR: v ax (cm-1) : 3330, 3163, 1746, 1729, 1654, 1612, 1582 1H NMR (DMS0-d5, 300MHz) (pp ) : 1.99-1.95 (3H, m, =NCH2CH2CH=) 2.00 (6H, s, -CH(CH2OCOCH3)2) 4.03 (4H, d, -CH(CH2OCOCH3)2) 4.14 (2H, t, =NCH2CH2CH=) 6.45 (2H, brs, -NH2)
8.09 (1H, s, H of C-8) 8.57 (1H, s, H of C-6)
Also, 0.19 g (1.2%) of 7- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine as a reaction byproduct was obtained (Rf=0.49).
Melting point: 137-139 °C
IR : vmax(cm_1) : 3330, 3160, 1743, 1728, 1645, 1606
1H NMR (DMSO-d6, 300MHz) (ppm) : 1.86-2.03 (9H, m, =NCH2CH2CH= and -CH (CH2OCOCH3) 2)
4.07 (4H, d, -CH(CH2OCOCH3)2)
4.16 (2H, t, =NCH2CH2CH=)
6.38 (2H, brs, -NH2)
8.06 (1H, s, H of C-8) 8.61 (1H, s, H of C-6)
Example 3j Preparation of 9- [4-acetoxy-3-
( acetoxymethyl) but-l-yl] -2-aminopurine
16.92 g (50 mmole) of 2-aminopurine-thallium salt was suspended in 140 ml of N, N-dimethylformamide, and the temperature of a reactor was maintained below 15 °C. The suspension was added slowly with a solution of 16.03 g (60 mmole) of 2-acetoxymethyl-4-bromobut-l-yl-acetate in 30 ml of N, N-dimethylformamide, followed by stirring for 84 hours at room temperature. At the end of the reaction, the stirred mixture was cooled and filtered, and then the filtrate was added with 100 ml of water. The solution was extracted three times with 70 ml of CHC13, and dried over magnesium sulfate, and then concentrated under reduced pressure to evaporate the solvent. The residue was crystallized from a mixed solvent of ethyl acetate, hexane and tert-butanol, to give 8.35 g (52%) of 9- [4-acetoxy-3- (acetoxymethyl) but- l-yl] -2-aminopurine. Spectrum data analyzed for the compound obtained in Example 3 were identical to Example 2.
Industrial Applicability
As can be seen from the foregoing, according to the process of the present invention, 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] -2-aminopurine (called
Famciclovir) of Formula (I) , a drug of purine derivatives having antiviral activity, can be prepared in a very high selectivity under mild reaction conditions while minimizing the production of 7- [4- acetoxy-3- (acetoxymethyl) but-l-yl-2-aminopurine of Formula (V) as a reaction byproduct.

Claims

Claims
1. A process for preparing a compound of Formula (I) , which comprises reacting a compound of Formula (XXI)' with a compound of Formula (III) in a polar organic solvent:
Figure imgf000014_0001
2. The process of Claim 1, wherein the polar organic solvent is at least one selected from the group consisting of N, -dimethylformamide, dimethylsulfoxide, lower alcoholic solvents with 1-3 carbon atoms, and a mixture thereof.
3. The process of Claim 1 or 2, wherein the reaction is carried out at a temperature of 0-100 °C.
4. The process of Claim 1, wherein the compound of Formula (XXI) is obtained by the reaction of a compound of Formula (II) with a compound of Formula (IV) :
Figure imgf000014_0002
(II) (IV)
5. The process of Claim 4, wherein the reaction is carried out in at least one polar organic solvent selected from the group consisting of N-dimethylformamide, dimethylsulfoxide, lower alcoholic solvents with 1-3 carbon atoms, and a mixture thereof.
6. The process of Claim 4 or 5, wherein the reaction is carried out at a temperature of 0-100 °C.
7. Use of thallium (I) ethoxide (TIOEt) for the preparation of 9- [4-acetoxy-3- (acetoxymethyl) but-l-yl] - 2-aminopurine of Formula (I) :
Figure imgf000015_0001
PCT/KR2003/001396 2002-07-15 2003-07-15 Process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine WO2004007497A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US10/521,352 US7041823B2 (en) 2002-07-15 2003-07-15 Process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine
AT03741578T ATE457987T1 (en) 2002-07-15 2003-07-15 METHOD FOR PRODUCING 9-[4-ACETOXY-3-(ACETOXYMETHYL)BUT-1-YL-2-AMINOPURINE
AU2003281046A AU2003281046B8 (en) 2002-07-15 2003-07-15 Process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine
JP2004521270A JP4231479B2 (en) 2002-07-15 2003-07-15 Process for producing 9- [4-acetoxy-3- (acetoxymethyl) but-1-yl] -2-aminopurine
DE60331334T DE60331334D1 (en) 2002-07-15 2003-07-15 PROCESS FOR PREPARING 9-i4-ACETOXY-3- (ACETOXYMETHYL) BUT-1-YL-2-AMINOPURINE
EP03741578A EP1551839B1 (en) 2002-07-15 2003-07-15 Process for preparing 9-¬4-acetoxy-3-(acetoxymethyl)but-1-yl -2-aminopurine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020020041267A KR100573859B1 (en) 2002-07-15 2002-07-15 A process for preparing 9-[4-acetoxy-3-acetoxymethylbut-1-yl]-2-aminopurine
KR10-2002-0041267 2002-07-15

Publications (1)

Publication Number Publication Date
WO2004007497A1 true WO2004007497A1 (en) 2004-01-22

Family

ID=30113179

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2003/001396 WO2004007497A1 (en) 2002-07-15 2003-07-15 Process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine

Country Status (8)

Country Link
US (1) US7041823B2 (en)
EP (1) EP1551839B1 (en)
JP (1) JP4231479B2 (en)
KR (1) KR100573859B1 (en)
AT (1) ATE457987T1 (en)
AU (1) AU2003281046B8 (en)
DE (1) DE60331334D1 (en)
WO (1) WO2004007497A1 (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102977171A (en) * 2012-12-18 2013-03-20 吉林大学 Five-membered heterocycle modified 4'-spiro nucleoside compounds and application in virus resistance
US9479322B2 (en) 2013-11-30 2016-10-25 Amir Keyvan Khandani Wireless full-duplex system and method using sideband test signals
US10177896B2 (en) 2013-05-13 2019-01-08 Amir Keyvan Khandani Methods for training of full-duplex wireless systems
US10211965B2 (en) 2012-05-13 2019-02-19 Amir Keyvan Khandani Full duplex wireless transmission with channel phase-based encryption
US10334637B2 (en) 2014-01-30 2019-06-25 Amir Keyvan Khandani Adapter and associated method for full-duplex wireless communication
US10333593B2 (en) 2016-05-02 2019-06-25 Amir Keyvan Khandani Systems and methods of antenna design for full-duplex line of sight transmission
US10700766B2 (en) 2017-04-19 2020-06-30 Amir Keyvan Khandani Noise cancelling amplify-and-forward (in-band) relay with self-interference cancellation
US11012144B2 (en) 2018-01-16 2021-05-18 Amir Keyvan Khandani System and methods for in-band relaying
US11057204B2 (en) 2017-10-04 2021-07-06 Amir Keyvan Khandani Methods for encrypted data communications

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100573861B1 (en) * 2003-07-18 2006-04-25 경동제약 주식회사 Preparing Methods for 2-Amino-9-2-halogenoethylpurine and 2-Amino-6,8-dichloro-9-2-hydroxyethylpurine as an Intermediate thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1205373A (en) * 1968-01-25 1970-09-16 Edward Curtis Taylor Chemical processes using organothallium compounds
US4020073A (en) * 1971-02-04 1977-04-26 Taylor Edward C Process for O-acylating thallus salts of 2-pyridone

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5684153A (en) * 1984-08-16 1997-11-04 Beecham Group Plc Process for the preparation of purine derivatives
GB8822236D0 (en) * 1988-09-21 1988-10-26 Beecham Group Plc Chemical process
GB9402161D0 (en) * 1994-02-04 1994-03-30 Wellcome Found Chloropyrimidine intermediates

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1205373A (en) * 1968-01-25 1970-09-16 Edward Curtis Taylor Chemical processes using organothallium compounds
US3626018A (en) * 1968-01-25 1971-12-07 Edward C Taylor Chemical processes using organothallium compounds
US4020073A (en) * 1971-02-04 1977-04-26 Taylor Edward C Process for O-acylating thallus salts of 2-pyridone

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10547436B2 (en) 2012-05-13 2020-01-28 Amir Keyvan Khandani Distributed collaborative signaling in full duplex wireless transceivers
US11757604B2 (en) 2012-05-13 2023-09-12 Amir Keyvan Khandani Distributed collaborative signaling in full duplex wireless transceivers
US11303424B2 (en) 2012-05-13 2022-04-12 Amir Keyvan Khandani Full duplex wireless transmission with self-interference cancellation
US10211965B2 (en) 2012-05-13 2019-02-19 Amir Keyvan Khandani Full duplex wireless transmission with channel phase-based encryption
US10742388B2 (en) 2012-05-13 2020-08-11 Amir Keyvan Khandani Full duplex wireless transmission with self-interference cancellation
CN102977171A (en) * 2012-12-18 2013-03-20 吉林大学 Five-membered heterocycle modified 4'-spiro nucleoside compounds and application in virus resistance
US10177896B2 (en) 2013-05-13 2019-01-08 Amir Keyvan Khandani Methods for training of full-duplex wireless systems
US10063364B2 (en) 2013-11-30 2018-08-28 Amir Keyvan Khandani Wireless full-duplex system and method using sideband test signals
US10374781B2 (en) 2013-11-30 2019-08-06 Amir Keyvan Khandani Wireless full-duplex system and method using sideband test signals
US9479322B2 (en) 2013-11-30 2016-10-25 Amir Keyvan Khandani Wireless full-duplex system and method using sideband test signals
US10334637B2 (en) 2014-01-30 2019-06-25 Amir Keyvan Khandani Adapter and associated method for full-duplex wireless communication
US10601569B2 (en) 2016-02-12 2020-03-24 Amir Keyvan Khandani Methods for training of full-duplex wireless systems
US11515992B2 (en) 2016-02-12 2022-11-29 Amir Keyvan Khandani Methods for training of full-duplex wireless systems
US11283494B2 (en) 2016-05-02 2022-03-22 Amir Keyvan Khandani Instantaneous beamforming exploiting user physical signatures
US10778295B2 (en) 2016-05-02 2020-09-15 Amir Keyvan Khandani Instantaneous beamforming exploiting user physical signatures
US10333593B2 (en) 2016-05-02 2019-06-25 Amir Keyvan Khandani Systems and methods of antenna design for full-duplex line of sight transmission
US10700766B2 (en) 2017-04-19 2020-06-30 Amir Keyvan Khandani Noise cancelling amplify-and-forward (in-band) relay with self-interference cancellation
US11265074B2 (en) 2017-04-19 2022-03-01 Amir Keyvan Khandani Noise cancelling amplify-and-forward (in-band) relay with self-interference cancellation
US11212089B2 (en) 2017-10-04 2021-12-28 Amir Keyvan Khandani Methods for secure data storage
US11146395B2 (en) 2017-10-04 2021-10-12 Amir Keyvan Khandani Methods for secure authentication
US11057204B2 (en) 2017-10-04 2021-07-06 Amir Keyvan Khandani Methods for encrypted data communications
US11012144B2 (en) 2018-01-16 2021-05-18 Amir Keyvan Khandani System and methods for in-band relaying

Also Published As

Publication number Publication date
KR100573859B1 (en) 2006-04-25
EP1551839B1 (en) 2010-02-17
KR20040007978A (en) 2004-01-28
ATE457987T1 (en) 2010-03-15
JP2005535672A (en) 2005-11-24
AU2003281046B2 (en) 2009-02-19
EP1551839A1 (en) 2005-07-13
US7041823B2 (en) 2006-05-09
DE60331334D1 (en) 2010-04-01
US20050222413A1 (en) 2005-10-06
JP4231479B2 (en) 2009-02-25
AU2003281046B8 (en) 2009-02-26
AU2003281046A1 (en) 2004-02-02

Similar Documents

Publication Publication Date Title
EP1883639B1 (en) Preparation of famciclovir and other purine derivatives
EP2125821A1 (en) Process for the preparation of sildenafil
EP1551839B1 (en) Process for preparing 9-¬4-acetoxy-3-(acetoxymethyl)but-1-yl -2-aminopurine
WO2007017468A2 (en) Preparation of a 7h-pyrr0l0 [2 , 3-d] pyrimidine derivative
EP1636231B1 (en) Methods for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine using a compound of 2-amino-9-(2-substituted ethyl)purines
JP2560358B2 (en) Imidazole derivative and process for producing the same
CN1471532A (en) Process for the preparation of z-alkoxy-6-trifluoromethyl-N-[(C1,2,4] triazolo[1,5-C] pyrimidin-2-yl) benzensulfonamides
JP4656604B2 (en) Inosine derivative and method for producing the same
KR102684954B1 (en) Novel intermediates useful for the synthesis of aminopyrimidine derivatives, process for preparing the same, and process for preparing aminopyrimidine derivatives using the same
CA2136885A1 (en) Process for preparing imidazopyridine derivatives
US6156892A (en) Purine derivatives having cyclopropane ring
JP2726653B2 (en) Diaminopyrimidine derivative
JPH0613477B2 (en) 5-hydrazino-1H-pyrazole compound
US4423219A (en) Production of purine derivatives and intermediates therefor
JP2815654B2 (en) Novel 4-substituted-3,5-dimethylpicolinic acid compound and method for producing the same
CA1122983A (en) Method of producing 5-fluorouracil derivatives
EP4116305A1 (en) Thienopyrimidine derivative and preparation method therefor
AU2011380598A1 (en) Method for preparing cyclopropane derivatives
EP1196399A1 (en) Process for the preparation of substituted benzisothiazole compounds
KR20070065653A (en) Process for preparing 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine
JPH07118232A (en) Production of indoloquinone derivative
JP2001278864A (en) Method for producing 4-methoxyquinolines
KR20010092426A (en) Method for producing 4-[(2&#39;,5&#39;-diamino-6&#39;-halopyrimidine-4&#39;-yl)amino]-cyclopent-2-enylmethanols

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2003741578

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2004521270

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 10521352

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2003281046

Country of ref document: AU

WWP Wipo information: published in national office

Ref document number: 2003741578

Country of ref document: EP