WO1993015075A1 - Preparation of 2-amino-6-chloropurine - Google Patents
Preparation of 2-amino-6-chloropurine Download PDFInfo
- Publication number
- WO1993015075A1 WO1993015075A1 PCT/GB1993/000185 GB9300185W WO9315075A1 WO 1993015075 A1 WO1993015075 A1 WO 1993015075A1 GB 9300185 W GB9300185 W GB 9300185W WO 9315075 A1 WO9315075 A1 WO 9315075A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- process according
- acyl group
- guanine
- chloropurine
- amino
- Prior art date
Links
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title description 5
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 10
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 6
- 230000007062 hydrolysis Effects 0.000 claims abstract description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical group ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- WJSVJNDMOQTICG-UHFFFAOYSA-N 2-amino-1-[(2-methyl-4-methylidene-5-oxooxolan-2-yl)methyl]-7h-purin-6-one Chemical compound NC1=NC=2N=CNC=2C(=O)N1CC1(C)CC(=C)C(=O)O1 WJSVJNDMOQTICG-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 229960004396 famciclovir Drugs 0.000 description 1
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- QNXFUWFRTWSSOK-UHFFFAOYSA-N n-acetyl-n-(6-oxo-3,7-dihydropurin-2-yl)acetamide Chemical compound O=C1NC(N(C(C)=O)C(=O)C)=NC2=C1NC=N2 QNXFUWFRTWSSOK-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229960001179 penciclovir Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- REJGOFYVRVIODZ-UHFFFAOYSA-N phosphanium;chloride Chemical class P.Cl REJGOFYVRVIODZ-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical group [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- NIUZJTWSUGSWJI-UHFFFAOYSA-M triethyl(methyl)azanium;chloride Chemical compound [Cl-].CC[N+](C)(CC)CC NIUZJTWSUGSWJI-UHFFFAOYSA-M 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
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
Definitions
- This invention relates to a process for the preparation of a compound useful as an intermediate in the preparation of pharmaceutical compounds.
- 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 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).
- EP-A-203685 (Beecham Group p.l.c.) describes a process for preparing a 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- acyl group by hydrolysis.
- phase transfer catalysts include tetrasubstituted ammonium chlorides.
- ammonium substituents include C2-12 aik i, usually C2-4 alkyl, or phenyl or benzyl.
- Other possible phase transfer catalysts include tetra-substituted phosphonium chlorides wherein examples of the substitutents are as defined above for ammonium chlorides.
- the phase transfer catalyst is tetraethylammonium chloride.
- 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 equivalents.
- a preferred chlorinating agent is phosphorus oxychloride.
- the chlorinating agent is present in an amount of from 2-10 preferably from 3-6 molar equivalents of the guanine derivative.
- the reaction may be effected in the presence of a weak base, such as a tertiary amine, for example N,N-dimethylanili ⁇ e or diethylaniline or triethylamine-
- a weak base such as a tertiary amine, for example N,N-dimethylanili ⁇ e or diethylaniline or triethylamine-
- the base is usually present in an approximately molar equivalent amount with respect to the guanine derivative.
- a catalytic amount of water may be added to the reaction mixture.
- added base may not be necessary, but is preferred.
- 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.
- reaction is allowed to proceed for a period of greater than half an hour, usually less than 30 hours.
- the compound of formula (I) may be prepared from 2,9-diacylguanine. Accordingly, the present invention provides 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.
- Aqueous sodium hydroxide is a suitable basic medium for the hydrolysis.
- Diacetyl guanine (8.0g, 0.034 moles), triethyimethylammonium chloride (15.45g, 0.102 moles), and triethylamine (4.74 mis, 0.034 moles) were heated together with stirring in acetonitrile (70mls) to 50°C.
- Phosphorus oxychioride (6.34 mis, 0.068 moles) was then added and stirring continued for 4 hours.
- the reaction mixture was cooled and then added to aqueous sodium hydroxide solution (20g in 300mls water).
- the reaction mixture was heated to 80°C for 2 hours and then the volume made up to 300 mis with water.
- the mixture was cooled to 25°C and the pH adjuster to 7 using 10% hydrochloric acid.
- the resulting slurry was stirred for fifteen minutes and the product filtered off and washed with water 30 mis and then dried at 80°C under vacuum to give a cream/off white coloured product.
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)
Abstract
A process for preparing 2-amino-6-chloropurine 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.
Description
Preparation of 2-am1 no-6-chloropurine
This invention relates to a process for the preparation of a compound useful as an intermediate in the preparation of pharmaceutical compounds.
The compound 2-amino-6-chloropurine of formula (I):
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 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).
EP-A-203685 (Beecham Group p.l.c.) describes a process for preparing a 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- acyl group by hydrolysis.
The reaction is preferably carried out in a polar inert organic solvent such as acetonitrile, tetrahydrofuran, dioxan, nitromethane, diglyme, dimethoxyethane, ordichloromethane. Acetonitrile is highly preferred.
Suitable phase transfer catalysts include tetrasubstituted ammonium chlorides. Examples of ammonium substituents include C2-12 aik i, usually C2-4 alkyl, or phenyl or benzyl. Other possible phase transfer catalysts include tetra-substituted phosphonium chlorides wherein examples of the substitutents are as defined above for ammonium chlorides. Preferably the phase transfer catalyst is tetraethylammonium chloride.
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 equivalents.
A preferred chlorinating agent is phosphorus oxychloride.
Preferably the chlorinating agent is present in an amount of from 2-10 preferably from 3-6 molar equivalents of the guanine derivative.
The reaction may be effected in the presence of a weak base, such as a tertiary amine, for example N,N-dimethylaniliπe or diethylaniline or triethylamine- The base is usually present in an approximately molar 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.
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.
Preferably the reaction is allowed to proceed for a period of greater than half an hour, usually less than 30 hours.
We have now discovered that the compound of formula (I) may be prepared from 2,9-diacylguanine.
Accordingly, the present invention provides 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.
The reaction is described in EP-A-203685 and EP-A-433846, which are incorporated herein by reference, except that methyltriethylammonium chloride is a preferred phase transfer catalyst; the amount of phosphorus oxychioride may be reduced to 2-4 equivalents, and the reaction time can be reduced.
If the removal of the 9-acyl group generally occurs at ambient temperature (below 30°C), but higher temperatures and reaction times (80-100°C, 1 -2 hours) are needed for removal of the 2-acyl group. Aqueous sodium hydroxide is a suitable basic medium for the hydrolysis.
The following example illustrates the invention.
Example
Diacetyl guanine (8.0g, 0.034 moles), triethyimethylammonium chloride (15.45g, 0.102 moles), and triethylamine (4.74 mis, 0.034 moles) were heated together with stirring in acetonitrile (70mls) to 50°C. Phosphorus oxychioride (6.34 mis, 0.068 moles) was then added and stirring continued for 4 hours. The reaction mixture was cooled and then added to aqueous sodium hydroxide solution (20g in 300mls water). The reaction mixture was heated to 80°C for 2 hours and then the volume made up to 300 mis with water. The mixture was cooled to 25°C and the pH adjuster to 7 using 10% hydrochloric acid. The resulting slurry was stirred for fifteen minutes and the product filtered off and washed with water 30 mis and then dried at 80°C under vacuum to give a cream/off white coloured product.
Weight 2-amino-6-chioropurine 4.69 g (74.6% yield).
Claims
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.
2. A process according to claim 1 , as described in EP-A-203685 and EP-A-433846.
3. A process according to claim 2, wherein the chlorinating agent is phosphorus oxychioride and the phase transfer catalyst is methyltriethyiammonium chloride.
4. A process according to in claim 3, wherein the amount of phosphorus oxychioride is 2-4 equivalents with respect to the 2,9-acylated guanine.
5. A process according to claim 1 , wherein aqueous sodium hydroxide is used as the basic medium for the hydrolysis.
6. A process according to claim 1 , substantially as described herein with reference to the Example.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP93902481A EP0625154A1 (en) | 1992-01-30 | 1993-01-28 | Preparation of 2-amino-6-chloropurine |
| KR1019940702650A KR950700299A (en) | 1992-01-30 | 1993-01-28 | Preparation of 2-amino-6-chlorpurine |
| AU33654/93A AU669874B2 (en) | 1992-01-30 | 1993-01-28 | Preparation of 2-amino-6-chloropurine |
| JP5513055A JPH07503246A (en) | 1992-01-30 | 1993-01-28 | Method for producing 2-amino-6-chloropurine |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9201961.1 | 1992-01-30 | ||
| GB929201961A GB9201961D0 (en) | 1992-01-30 | 1992-01-30 | Pharmaceuticals |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1993015075A1 true WO1993015075A1 (en) | 1993-08-05 |
Family
ID=10709516
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1993/000185 WO1993015075A1 (en) | 1992-01-30 | 1993-01-28 | Preparation of 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) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0590361A1 (en) * | 1992-09-17 | 1994-04-06 | BASF Aktiengesellschaft | Process for the preparation of 2-amino-6-halopurines |
| EP0644193A3 (en) * | 1993-09-17 | 1995-04-12 | Juzen Chemical Co Ltd | Process for preparing 2-acetylamino-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 |
| EP0773220A1 (en) * | 1995-11-09 | 1997-05-14 | SUMIKA FINE CHEMICALS Co., Ltd. | 2-Amino-6-chloropurine and method for preparing the same |
| WO2003084958A1 (en) * | 2002-04-04 | 2003-10-16 | Sumitomo Chemical Company, Limited | Production method of 2,6-dihalopurine |
| CN102336755A (en) * | 2011-09-30 | 2012-02-01 | 浙江工业大学 | Chemical synthesis method of 6-chloropurine |
| CN113214260A (en) * | 2021-05-10 | 2021-08-06 | 上海凌凯医药科技有限公司 | Synthesis method of 2-acetamido-9-acetyl purine |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0141927A2 (en) | 1983-08-18 | 1985-05-22 | Beecham Group Plc | Antiviral guanine derivatives |
| EP0182024A2 (en) | 1984-09-20 | 1986-05-28 | Beecham Group Plc | Purine derivatives and their pharmaceutical use |
| EP0203685A2 (en) | 1985-03-23 | 1986-12-03 | Beecham Group Plc | Process for the preparation of 2-amino-6-chloro-purine |
| EP0433846A1 (en) | 1989-12-16 | 1991-06-26 | Hoechst Aktiengesellschaft | Process for the preparation of 2-acylamino-6-halogeno-purine from 2,9-diacylguanine |
| EP0433845A1 (en) * | 1989-12-16 | 1991-06-26 | Hoechst Aktiengesellschaft | Process for the preparation of 2-acylamino-9-acyl-6-halogeno-purines |
| WO1992013859A1 (en) * | 1991-01-31 | 1992-08-20 | Smithkline Beecham Plc | Pharmaceuticals |
-
1992
- 1992-01-30 GB GB929201961A patent/GB9201961D0/en active Pending
-
1993
- 1993-01-28 EP EP93902481A patent/EP0625154A1/en not_active Withdrawn
- 1993-01-28 KR KR1019940702650A patent/KR950700299A/en not_active Withdrawn
- 1993-01-28 NZ NZ246677A patent/NZ246677A/en unknown
- 1993-01-28 CA CA002117435A patent/CA2117435A1/en not_active Abandoned
- 1993-01-28 ZA ZA93615A patent/ZA93615B/en unknown
- 1993-01-28 WO PCT/GB1993/000185 patent/WO1993015075A1/en not_active Application Discontinuation
- 1993-01-28 MX MX9300482A patent/MX9300482A/en unknown
- 1993-01-28 JP JP5513055A patent/JPH07503246A/en active Pending
- 1993-01-28 AU AU33654/93A patent/AU669874B2/en not_active Ceased
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0141927A2 (en) | 1983-08-18 | 1985-05-22 | Beecham Group Plc | Antiviral guanine derivatives |
| EP0182024A2 (en) | 1984-09-20 | 1986-05-28 | Beecham Group Plc | Purine derivatives and their pharmaceutical use |
| EP0203685A2 (en) | 1985-03-23 | 1986-12-03 | Beecham Group Plc | Process for the preparation of 2-amino-6-chloro-purine |
| EP0433846A1 (en) | 1989-12-16 | 1991-06-26 | Hoechst Aktiengesellschaft | Process for the preparation of 2-acylamino-6-halogeno-purine from 2,9-diacylguanine |
| EP0433845A1 (en) * | 1989-12-16 | 1991-06-26 | Hoechst Aktiengesellschaft | Process for the preparation of 2-acylamino-9-acyl-6-halogeno-purines |
| WO1992013859A1 (en) * | 1991-01-31 | 1992-08-20 | Smithkline Beecham Plc | Pharmaceuticals |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0590361A1 (en) * | 1992-09-17 | 1994-04-06 | BASF Aktiengesellschaft | Process for the preparation of 2-amino-6-halopurines |
| EP0644193A3 (en) * | 1993-09-17 | 1995-04-12 | Juzen Chemical Co Ltd | Process for preparing 2-acetylamino-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 |
| EP0773220A1 (en) * | 1995-11-09 | 1997-05-14 | SUMIKA FINE CHEMICALS Co., Ltd. | 2-Amino-6-chloropurine and method for preparing the same |
| US5789590A (en) * | 1995-11-09 | 1998-08-04 | Sumika Fine Chemicals Co., Ltd. | Double cone-like crystal form of 2-amino-6-chloropurine and preparation |
| US6187921B1 (en) | 1995-11-09 | 2001-02-13 | Sumika Fine Chemicals Co., Ltd. | 2-amino-6-chloropurine and method for preparing the same |
| WO2003084958A1 (en) * | 2002-04-04 | 2003-10-16 | Sumitomo Chemical Company, Limited | Production method of 2,6-dihalopurine |
| CN1314685C (en) * | 2002-04-04 | 2007-05-09 | 住友化学工业株式会社 | Production method of 2,6-dihalopurine |
| US7307167B2 (en) | 2002-04-04 | 2007-12-11 | Sumitomo Chemical Company, Limited | Production method of 2,6-dihalopurine |
| CN102336755A (en) * | 2011-09-30 | 2012-02-01 | 浙江工业大学 | Chemical synthesis method of 6-chloropurine |
| CN113214260A (en) * | 2021-05-10 | 2021-08-06 | 上海凌凯医药科技有限公司 | Synthesis method of 2-acetamido-9-acetyl purine |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2117435A1 (en) | 1993-08-05 |
| AU3365493A (en) | 1993-09-01 |
| ZA93615B (en) | 1993-11-26 |
| EP0625154A1 (en) | 1994-11-23 |
| JPH07503246A (en) | 1995-04-06 |
| KR950700299A (en) | 1995-01-16 |
| AU669874B2 (en) | 1996-06-27 |
| GB9201961D0 (en) | 1992-03-18 |
| NZ246677A (en) | 1996-02-27 |
| MX9300482A (en) | 1994-07-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6870053B2 (en) | Chloropyrimidine intermediates | |
| EP0569421B1 (en) | Process for the preparation of 2-amino-6-chloropurine and derivatives | |
| AU669874B2 (en) | Preparation of 2-amino-6-chloropurine | |
| EP0203685B1 (en) | Process for the preparation of 2-amino-6-chloro-purine | |
| AU634564B2 (en) | Process for preparing 2,5-diamino-4,6-dichloropyrimidine | |
| JP2672874B2 (en) | Manufacturing method of cytosine | |
| US5663338A (en) | Process for preparing 2-amino-6-chloropurine | |
| JPH0645620B2 (en) | Method for methylating xanthines | |
| CA1330080C (en) | Process for precipitating cytosine from alkaline solutions with sulphuric acid | |
| GB2160204A (en) | Preparation of N-methyl-1-alkylthio-2-nitroethenamines | |
| JPH07300480A (en) | Improved process for the preparation of 2-amino-6-chloropurine and 2-acylamino-6-chloropurine | |
| JPH0212231B2 (en) | ||
| JPH0578358A (en) | New method for preparing and purififying compound | |
| JP2002069050A (en) | Method for producing hydrazocarbonamide | |
| CS263369B1 (en) | New 5-halogen-6-amino-1-methyluracil derivatives and process for preparing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA JP KR NZ US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 1993902481 Country of ref document: EP |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 246677 Country of ref document: NZ |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2117435 Country of ref document: CA |
|
| ENP | Entry into the national phase |
Ref document number: 1994 256918 Country of ref document: US Date of ref document: 19940729 Kind code of ref document: A |
|
| WWP | Wipo information: published in national office |
Ref document number: 1993902481 Country of ref document: EP |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 1993902481 Country of ref document: EP |