NZ246677A - Preparatory process for 2-amino-6-chloropurine - Google Patents
Preparatory process for 2-amino-6-chloropurineInfo
- Publication number
- NZ246677A NZ246677A NZ246677A NZ24667793A NZ246677A NZ 246677 A NZ246677 A NZ 246677A NZ 246677 A NZ246677 A NZ 246677A NZ 24667793 A NZ24667793 A NZ 24667793A NZ 246677 A NZ246677 A NZ 246677A
- Authority
- NZ
- New Zealand
- Prior art keywords
- chloropurine
- amino
- acyl group
- guanine
- hydrolysis
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
<div class="application article clearfix" id="description">
<p class="printTableText" lang="en">New Zealand Paient Spedficaiion for Paient Number £46677 <br><br>
24 6 6 7 7 <br><br>
New Zealand No. 246677 International No. PCT/GB93/00185 <br><br>
TO BE ENTERED AFTER ACCEPTANCE AND PUBLICATION <br><br>
Priority dates; 2><=> \ \ \ R *3. Intemational fifing date: 28) I) <33> Classification:; ?cL>\ Cci id un 2>/ M-O. Publication date: 2 7 FEB 1996 Journal No.: , i i ^ . <br><br>
NEWZE^IAKD PATENTS ACT 1953 <br><br>
• COMPLETE SPECIFICATION <br><br>
Tide of invention: <br><br>
PREPARATION OF 2-AMINO-6-CHLOROPURINE <br><br>
Name, address and nationality of applicant(s) as in international application fonn: <br><br>
SMITHKLINE BEECHAM pic, a British company of New Horizons Court, Brentford, Middlesex TW8 9EP, United Kingdom. <br><br>
WO 93/15075 <br><br>
246 67 7 <br><br>
PCT/GB93/00185 <br><br>
-1- <br><br>
Preparation of 2-am1no-6-chloropur1ne <br><br>
This invention relates to a process for the preparation of a compound useful 5 as an intermediate in the preparation of pharmaceutical compounds. <br><br>
The compound 2-amino-6-chloropurine of formula (I): <br><br>
CI <br><br>
is a useful intermediate in the preparation of nucleoside analogue antiviral agents, such as penciclovir and famciclovir, described in EP-A-141927 (Example 1) and EP-A-182024 (Example 2). The intermediate is 15 9-substituted with an appropriate side chain precursor, followed by conversion of the 6-chloro moiety to a hydroxy (a guanine) or hydrogen (a 2-aminopurine). <br><br>
EP-A-203685 (Beecham Group p.l.c.) describes a process for preparing a 20 compound of formula (I) as hereinbefore defined, which process comprises reacting guanine with a chlorinating agent in the presence of a phase transfer catalyst containing chloride ions. EP-A-433846 (Hoechst Aktiengesellschaft) describes a corresponding process for preparing the 2-acylated derivative, involving chlorination of 2,9-diacylguanine and subsequent removal of the 9-25 acyl group by hydrolysis. <br><br>
The reaction is preferably carried out in a polar inert organic solvent such as acetonitrile.tetrahydrofuran, dioxan, nitromethane, diglyme, dimethoxyethane, or dichloromethane. Acetonitrile is highly preferred. <br><br>
30 <br><br>
246677 <br><br>
O 93/15075 PCT/GB93/00185 <br><br>
-2- <br><br>
Suitable phase transfer catalysts include tetrasubstituted ammonium chlorides. Examples of ammonium substituents include C2-12 a'kytf usually C2-4 alkyl, or phenyl or benzyl. Other possible phase transfer catalysts include tetra-substituted phosphonium chlorides wherein examples of the 5 substitutents are as defined above for ammonium chlorides. Preferably the phase transfer catalyst is tot. aethylammonium chloride. <br><br>
The phase-transfer catalyst is preferably present in an amount of from 1 to 3 equivalents of the compound of formula (II) and preferably from 1 to 2 10 equivalents. <br><br>
A preferred chlorinating agent is phosphorus oxychloride. <br><br>
Preferably the chlorinating agent is present in an amount of from 2-10 15 preferably from 3-6 molar equivalents of the guanine derivative. <br><br>
The reaction may be effected in the presence of a weak base, such as a tertiary amine, for example N,N-dimethylaniline or diethylamide or triethylamine. The base is usually present in an approximately molar 20 equivalent amount with respect to the guanine derivative. Alternatively, a catalytic amount of water may be added to the reaction mixture. When acetonitrile is the solvent, added base may not be necessary, but is preferred. <br><br>
25 The reaction is preferably carried out at an elevated temperature of from 30-100°C, most preferably under reflux and/or with ultrasonication at 50-70°C. <br><br>
Preferably the reaction is allowed to proceed for a period of greater than half 30 an hour, usually less than 30 hours. <br><br>
We have now discovered that the compound of formula (I) may be prepared from 2,9-diacyiguanine. <br><br></p>
</div>
Claims (7)
1. A process for preparing 2-amino-6-chloropurine, which process comprises reacting a 2,9-diacylated derivative of guanine with a chlorinating agent in the presence of a phase transfer catalyst containing chloride ions, and thereafter removing the 9-acyl group and the 2-acyl group by hydrolysis.<br><br>
2. A process according to claim 1, wherein the chlorinating agent is phosphorus oxychloride and the phase transfer catalyst is methyltriethylammonium chloride.<br><br>
3. A process according to claim 2, wherein the amount of phosphorus oxychloride is 2-4 equivalents with respect to the 2,9-acylated guanine.<br><br>
4. A process according to any one of claims 1 to 3, wherein aqueous sodium hydroxide is used as a basic medium for the hydrolysis.<br><br>
5. Famciclovir or penciclovir whenever prepared from 2-amino-6-chloropurine prepared by the process of any one of claims 1 to 4.<br><br>
6. A process according to claim 1, substantially as described herein with reference to the Example.<br><br>
7. 2-Amino-6-chloropurine whenever prepared according to the process of any one of claims 1 to 4. .<br><br> By the authorised agents A J PARK & S<br><br> </p> </div>
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB929201961A GB9201961D0 (en) | 1992-01-30 | 1992-01-30 | Pharmaceuticals |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ246677A true NZ246677A (en) | 1996-02-27 |
Family
ID=10709516
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ246677A NZ246677A (en) | 1992-01-30 | 1993-01-28 | Preparatory process for 2-amino-6-chloropurine |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP0625154A1 (en) |
JP (1) | JPH07503246A (en) |
KR (1) | KR950700299A (en) |
AU (1) | AU669874B2 (en) |
CA (1) | CA2117435A1 (en) |
GB (1) | GB9201961D0 (en) |
MX (1) | MX9300482A (en) |
NZ (1) | NZ246677A (en) |
WO (1) | WO1993015075A1 (en) |
ZA (1) | ZA93615B (en) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4231036A1 (en) * | 1992-09-17 | 1994-03-24 | Basf Ag | Process for the preparation of 2-amino-6-halopurines |
JPH07133276A (en) * | 1993-09-17 | 1995-05-23 | Jiyuuzen Kagaku Kk | Production of 2-acetylamono-6-chloropurine |
DE4415196C1 (en) * | 1994-04-30 | 1995-04-27 | Boehringer Ingelheim Kg | Improved process for the preparation of 2-amino-6-chloropurine and 2-acylamino-6-chloropurines |
CA2189088C (en) | 1995-11-09 | 2005-09-20 | Masatoshi Sakai | 2-amino-6-chloropurine and method for preparing the same |
JP4223408B2 (en) | 2002-04-04 | 2009-02-12 | 住友化学株式会社 | Method for producing 2,6-dihalopurine |
CN102336755B (en) * | 2011-09-30 | 2013-03-27 | 浙江工业大学 | Chemical synthesis method of 6-chloropurine |
CN113214260B (en) * | 2021-05-10 | 2022-04-01 | 上海凌凯医药科技有限公司 | Synthesis method of 2-acetamido-9-acetyl purine |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3485225D1 (en) | 1983-08-18 | 1991-12-05 | Beecham Group Plc | ANTIVIRAL GUANINE DERIVATIVES. |
DE3582399D1 (en) | 1984-09-20 | 1991-05-08 | Beecham Group Plc | PURINE DERIVATIVES AND THEIR PHARMACEUTICAL USE. |
GB8507606D0 (en) * | 1985-03-23 | 1985-05-01 | Beecham Group Plc | Process |
DE3941657A1 (en) | 1989-12-16 | 1991-06-20 | Hoechst Ag | METHOD FOR PRODUCING 2-ACYLAMINO-6-HALOGEN PURINE FROM 2,9-DIACYLGUANINE |
DE3941658A1 (en) * | 1989-12-16 | 1991-06-20 | Hoechst Ag | METHOD FOR PRODUCING 2-ACYLAMINO-9-ACYL-6-HALOGEN PURIN |
GB9102127D0 (en) * | 1991-01-31 | 1991-03-13 | Smithkline Beecham Plc | Pharmaceuticals |
-
1992
- 1992-01-30 GB GB929201961A patent/GB9201961D0/en active Pending
-
1993
- 1993-01-28 WO PCT/GB1993/000185 patent/WO1993015075A1/en not_active Application Discontinuation
- 1993-01-28 ZA ZA93615A patent/ZA93615B/en unknown
- 1993-01-28 AU AU33654/93A patent/AU669874B2/en not_active Ceased
- 1993-01-28 CA CA002117435A patent/CA2117435A1/en not_active Abandoned
- 1993-01-28 JP JP5513055A patent/JPH07503246A/en active Pending
- 1993-01-28 KR KR1019940702650A patent/KR950700299A/en not_active Application Discontinuation
- 1993-01-28 NZ NZ246677A patent/NZ246677A/en unknown
- 1993-01-28 MX MX9300482A patent/MX9300482A/en unknown
- 1993-01-28 EP EP93902481A patent/EP0625154A1/en not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
EP0625154A1 (en) | 1994-11-23 |
AU669874B2 (en) | 1996-06-27 |
AU3365493A (en) | 1993-09-01 |
ZA93615B (en) | 1993-11-26 |
GB9201961D0 (en) | 1992-03-18 |
CA2117435A1 (en) | 1993-08-05 |
KR950700299A (en) | 1995-01-16 |
JPH07503246A (en) | 1995-04-06 |
WO1993015075A1 (en) | 1993-08-05 |
MX9300482A (en) | 1994-07-29 |
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