WO2005058925A1 - New process for preparing diisopropyl ((1-((2-amino-6-halo-9h-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonate - Google Patents
New process for preparing diisopropyl ((1-((2-amino-6-halo-9h-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonate Download PDFInfo
- Publication number
- WO2005058925A1 WO2005058925A1 PCT/KR2004/003257 KR2004003257W WO2005058925A1 WO 2005058925 A1 WO2005058925 A1 WO 2005058925A1 KR 2004003257 W KR2004003257 W KR 2004003257W WO 2005058925 A1 WO2005058925 A1 WO 2005058925A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- compound
- amino
- new process
- purin
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 title description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 title description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-L methylphosphonate(2-) Chemical compound CP([O-])([O-])=O YACKEPLHDIMKIO-UHFFFAOYSA-L 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 13
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 125000002346 iodo group Chemical group I* 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 abstract description 4
- 208000002672 hepatitis B Diseases 0.000 abstract description 3
- 239000003443 antiviral agent Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 239000002777 nucleoside Substances 0.000 abstract description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 2
- 230000003612 virological effect Effects 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 8
- -1 AZT Chemical class 0.000 description 7
- 239000006227 byproduct Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-M methylphosphonate(1-) Chemical compound CP(O)([O-])=O YACKEPLHDIMKIO-UHFFFAOYSA-M 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- CQYPNVKLVHHOSJ-UHFFFAOYSA-N 6-iodo-7h-purin-2-amine Chemical compound NC1=NC(I)=C2NC=NC2=N1 CQYPNVKLVHHOSJ-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- XIPUIGPNIDKXJU-UHFFFAOYSA-N [CH]1CC1 Chemical compound [CH]1CC1 XIPUIGPNIDKXJU-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
Definitions
- the compound of formula (2) is a stock medicine substance which is devebped as new therapeutic agent for hepatitis B (Korean Patent Application No. KR2002-0003051, WO 02/057288) and is the most important intermediate for preparation of the compound of formula (2).
- Purine derivative such as formula (2) has anticancer and antiviral activity, and 10 or more kinds of compounds including AZT, 3TC, ACN, etc. are on the market.
- selectivity between two nitrogens of imidazole ring is always present in introducing purine radical, there have been a number of studies to solve this problem (Tetrahedron, 199ft 46, 6903; Helv. Chim. Acta, 1989, 72, 1495; J. Org. Chem., 1995, 60, 2902; EP 0967213).
- R and R are as defined above,
- R and R are as defined above,
- R and R are as defined above,
- the present inventors have performed extensive studies to obtain the compound cf formula (1) in high yield. As a result, the inventors have found out that selectivity to the objective compound of formula (1) and stability of the compound of formula (3) are improved and formation of by-products is reduced by using weak base, cesium carbonate, as base.
- the present invention relates to a process for preparing the compound cf formula (1), salt, hydrate, or solvate thereof by reacting the compound of formula (3) with 2-amino-6-habpurine of the following formula (7) in the presence of cesium carbonate as base.
- X represents habgen, for example fluoro, chbro, bromo, or iodo.
- selectivity to the compound cf formula (1) and stability cf starting material, the compound cf formula (3) can be improved by using cesium carbonate as base, and formation cf by-productes cf formula (6) having two purine structures can be reduced by controlling the amount cf base.
- the process can be carried out under mild conditions by using weak base, cesium carbonate, and thus formation of by-products cf formula (6) can be further reduced. Therefore, selectivity, stability cf the compound cf formula (3), and formantion cf by-products caused by overreaction which are disadvantages cf the prior process can be overcome by the present invention.
- a suspension of 2-amino-6-habpurine compound of formula (7) in DMF is treated with cesium carbonate and mesylate compound of formula (3) to give the compound of formula (1).
- the compound of formula (7) is used in an amount of 1.1 to 2.0 equivalents, preferably 1.3 to 1.7 equivalents based on the compound of formula (3).
- 2-amino-6-iodopurine compound can be preferably used. It is more preferred to use the compound substituted by relatively large iodo in 6-position to reduce the production rate of N-7 isomer due to steric hindrance.
- DMF which is used to prepare the suspension is used in an amount of 2.8 to 12.3 g, preferably 2.8 to 6.5 g per g, of the compound of formula (3).
- Cesium carbonate is used in an amount of not more than 3.0 equivalents, preferably 1.1 to 2.2 equivalents, particulary preferably 1.2 to 1.7 equivalents, based on the compound of formula (3).
- cesium carbonate is used in an amount of more than 3.0 equivalents, by-products of formula (6) having two purines are formed.
- the reaction solution is stirred at room temperature for 20 minutes, and 1.0 equivalent of the compound of formula (3) is added dropwise to the solution.
- the solution is further reacted at room temperature for about 10 to 24 hours, and then the reaction mixture is quenched with water.
- the selectivity ratio of the objective compound of formula (1) to N-7 isomer, the compound of formula (5), is 6:1 to 9:1.
- the selectivity can be increased to 25:1 by washing the organic layer with diluted sulfuric acid.
- the objective compound of formula (1) can be obtained in pure form by recrys- tallization with ether.
- decomposition tendency of mesybxy of the compound of formula (3) may be different, depending upon base strength to be used.
- weak base such as cesium carbonate
- the decomposition of the compound of formula (3) can be reduced, compared with strong base such as sodium hydride (monitored by HPLC analysis). Therefore, it is considered that stability of the starting material, the compound of formula (3), can be improved by using weak base, cesium carbonate, according to the present invention.
Abstract
The present invention relates to a new process for preparing the compound of formula (1) which is important intermediate for preparation of nucleoside analog of the compound of formula (2) effective as antiviral agent, in particular hepatitis B viral agent.
Description
Description NEW PROCESS FOR PREPARING DIISOPROPYL ((l-((2-AMINO-6-HALO-9H-PURIN-9-YL)METHYL)CYCLOPRO PYL)OXY)METHYLPHOSPHONATE [i] [2] TECHiNICAL FIELD [3] [4] The present invention relates to a new process for preparing the ccmpcund of the following formula (1) [5]
[10] [11] which is important intermediate for preparation of nucleoside analog of the ccmpcund of the following formula (2) [12]
[13]
[14] effective as antiviral agent, in particular hepatitis B viral agent.
[15]
[16] BACKGROUND ART
[17]
[18] The compound of formula (2) is a stock medicine substance which is devebped as new therapeutic agent for hepatitis B (Korean Patent Application No. KR2002-0003051, WO 02/057288) and is the most important intermediate for preparation of the compound of formula (2). Purine derivative such as formula (2) has anticancer and antiviral activity, and 10 or more kinds of compounds including AZT, 3TC, ACN, etc. are on the market. However, since selectivity between two nitrogens of imidazole ring is always present in introducing purine radical, there have been a number of studies to solve this problem (Tetrahedron, 199ft 46, 6903; Helv. Chim. Acta, 1989, 72, 1495; J. Org. Chem., 1995, 60, 2902; EP 0967213).
[19]
[20] A prior process known in Korean Patent Application No. KR2002-0003051 and WO 02/057288 prepares the objective compound of the above formula (1), N-7 isomer, the compound of the following formula (5),
[21]
[22]
[23] in which 1 2
[24] R and R are as defined above,
[25]
[26] and the compound of the following formula (6)
[27]
[29] in which 1 2
[30] R and R are as defined above,
[31]
[32] which is a reactant of two molecules cf purine, in a ratio of 2.5 : 1 : 1 by reacting { l-[(diisopropo5^phosphoryl)methoxy]cycfopropyl}methylmethane sulfonate of the following formula (3)
[33]
[34]
[35] in which 1 2
[36] R and R are as defined above,
[37]
[38] with 2-amino-6-chforopurine of the following formula (4),
[39]
[41] in the presence cf sodium hydride as base.
[42]
[43] The above process can be illustrated by the following Reaction Scheme (1).
[44]
[45] Reaction Scheme 1
[46]
[47]
[48] However, the process has a couple of disadvantages such as low selectivity and formation of by-products. Moreover, stability of the compound of formula (3) is limited. Thus, there has been a need to overcome these problems.
[49]
[50] DISCLOSURE OF THE INVENTION
[51]
[52] The present inventors have performed extensive studies to obtain the compound cf formula (1) in high yield. As a result, the inventors have found out that selectivity to the objective compound of formula (1) and stability of the compound of formula (3) are improved and formation of by-products is reduced by using weak base, cesium carbonate, as base.
[53]
[54] Therefore, an object of the present invention is to provide a new process for preparing the compound of formula (1) by changing the reaction conditions.
[55]
[56] The present invention relates to a process for preparing the compound cf formula (1), salt, hydrate, or solvate thereof by reacting the compound of formula (3) with 2-amino-6-habpurine of the following formula (7) in the presence of cesium carbonate as base.
[57]
[58]
[59] in which
[60] X represents habgen, for example fluoro, chbro, bromo, or iodo.
[61]
[62] When X represents iodo, the process according to the present invention can be illustrated by the following Reaction Scheme (2). [63]
[64] Reaction Scheme 2
[65]
[66]
[67] In the present invention, selectivity to the compound cf formula (1) and stability cf starting material, the compound cf formula (3), can be improved by using cesium carbonate as base, and formation cf by-productes cf formula (6) having two purine structures can be reduced by controlling the amount cf base. In addition, the process can be carried out under mild conditions by using weak base, cesium carbonate, and thus formation of by-products cf formula (6) can be further reduced. Therefore, selectivity, stability cf the compound cf formula (3), and formantion cf by-products caused by overreaction which are disadvantages cf the prior process can be overcome by the present invention.
[68]
[69] Befow, the present invention is illustrated in more detail.
[70]
[71] BEST MODE FOR CARRYING OUT THE INVENTION
[72]
[73] A suspension of 2-amino-6-habpurine compound of formula (7) in DMF is treated with cesium carbonate and mesylate compound of formula (3) to give the compound of formula (1). The compound of formula (7) is used in an amount of 1.1 to 2.0
equivalents, preferably 1.3 to 1.7 equivalents based on the compound of formula (3). Among the compound of formula (7), 2-amino-6-iodopurine compound can be preferably used. It is more preferred to use the compound substituted by relatively large iodo in 6-position to reduce the production rate of N-7 isomer due to steric hindrance. In addition, DMF which is used to prepare the suspension is used in an amount of 2.8 to 12.3 g, preferably 2.8 to 6.5 g per g, of the compound of formula (3). Cesium carbonate is used in an amount of not more than 3.0 equivalents, preferably 1.1 to 2.2 equivalents, particulary preferably 1.2 to 1.7 equivalents, based on the compound of formula (3). When cesium carbonate is used in an amount of more than 3.0 equivalents, by-products of formula (6) having two purines are formed. The reaction solution is stirred at room temperature for 20 minutes, and 1.0 equivalent of the compound of formula (3) is added dropwise to the solution. The solution is further reacted at room temperature for about 10 to 24 hours, and then the reaction mixture is quenched with water. The selectivity ratio of the objective compound of formula (1) to N-7 isomer, the compound of formula (5), is 6:1 to 9:1. The selectivity can be increased to 25:1 by washing the organic layer with diluted sulfuric acid. Furthermore, the objective compound of formula (1) can be obtained in pure form by recrys- tallization with ether.
[74]
[75] In particular, decomposition tendency of mesybxy of the compound of formula (3) may be different, depending upon base strength to be used. Thus, by using weak base such as cesium carbonate, the decomposition of the compound of formula (3) can be reduced, compared with strong base such as sodium hydride (monitored by HPLC analysis). Therefore, it is considered that stability of the starting material, the compound of formula (3), can be improved by using weak base, cesium carbonate, according to the present invention.
[76]
[77] The compound of formula (1) prepared in the above manner can be subjected to conventional conversion process to give salt, hydrate, or solvate, of the compound of formula (1).
[78]
[79] The following examples are presented to illustrate further the present invention. However, it should be understood that these examples are intended to illustrate the present invention, and cannot limit the technical scope of the present invention .
[80]
[81] Example 1
[82] Preparation of diisopropyl ({l-[(2-amino-6-iodo-9H-purin-9-yl)methyl] cyclo-propyl}oxy)methylphosphonate (1)
[83]
[84] 2-Amino-6-iodopurine (9.8 g, 37.5 mmol) was suspended in DMF (30 mH ) at room temperature, cesium carbonate (11.8 g, 37.5 mmol) was added dropwise thereto, and then stirred at room temperature for about 20 minutes. To the mixture was added dropwise { 1 - [(diisopropoxyphosphoryl)methoxy] cycbpropyl } methylmethanesulfonate (10 g, 29.0 mmol), and the mixture was stirred at room temperature for about 19 hours, while it was monitored by HPLC. To the mixtute was added water (90 mil ) to complete the reaction, and the reaction mixture was extracted with ethyl acetate (3 x 60 M ). Extracted organic layer was washed with water (90 M ), IN sulfiiric acid (90 M ), and 5% aqueous ammonium chbride solution (90 M ) in turn, and the resulting organic layer was distilled under reduced pressure in vacuo. To the resultant was added ethyl ether (100 mβ ), and then stirred at 0 °C for 15 hours to give the title compound as solid (7.1 g, yield of 48%, purity of 96%).
[85] 1
[86] H NMR (CDC1 ) δ: 0.83~0.88(m, 2H), 1.02~1.05(m, 2H), 1.25(d, J=4.5Hz, 6H), 3 1.30(d, J=4.5Hz, 6H), 3.83(d, J=7.SIz, 2H), 4.20(s, 2H), 4.70(m, 2H), 5.09(s, NH , 2 2H), 8.14(s, 1H) [87] [88] EFFECT OF THE INVENTION
[89]
[90] The selectivity, stability of the compound of formula (3), and formation of byproducts caused by overreaction, which are disadvantages of the prior process, can be improved, and thus the total yield can be increased by using cesium carbonate as base according to the present process.
Claims
[ 1 ] 1. A process for preparing the compound of the following formula ( 1 ), salt, hydrate, or solvate thereof
[3] characterized in that the compound of the following formula (3)
[5] is reacted with 2-amino-6-habpurine of the following formula (7)
[7] in the presence of cesium carbonate as base.
[8] 2. The process according to claim 1 wherein X represents iodo.
[9] 3. The process according to claim 1 wherein 2-amino-6-habpurine of formula (7) is empbyed from 1.1 to 2.0 equivalents based on the compound of formula (3). [10] 4. The process according to claim 1 wherein cesium carbonate is empbyed from 1.1 to 2.2 equivalents based on the compound of formula (3).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020030093942A KR20050062940A (en) | 2003-12-19 | 2003-12-19 | New process for preparing diisopropyl ((1-((2-amino-6-halo-9h-purin-9-yl)methyl)cyclopropyl)oxy)-methylphosphonate |
| KR10-2003-0093942 | 2003-12-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2005058925A1 true WO2005058925A1 (en) | 2005-06-30 |
Family
ID=36603117
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2004/003257 WO2005058925A1 (en) | 2003-12-19 | 2004-12-10 | New process for preparing diisopropyl ((1-((2-amino-6-halo-9h-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonate |
Country Status (4)
| Country | Link |
|---|---|
| KR (1) | KR20050062940A (en) |
| AR (1) | AR046948A1 (en) |
| TW (1) | TW200526225A (en) |
| WO (1) | WO2005058925A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8093229B2 (en) | 2005-03-30 | 2012-01-10 | Conforma Therapeutics Corporation | Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs as HSP90-inhibitors |
| US8710047B2 (en) | 2008-05-29 | 2014-04-29 | Albany Molecular Research, Inc. | 5-HT3 receptor modulators, methods of making, and use thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5302585A (en) * | 1990-04-20 | 1994-04-12 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Use of chiral 2-(phosphonomethoxy)propyl guanines as antiviral agents |
| US5977089A (en) * | 1996-07-26 | 1999-11-02 | Gilead Sciences, Inc. | Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability |
| EP0967213A1 (en) * | 1998-06-23 | 1999-12-29 | SUMIKA FINE CHEMICALS Co., Ltd. | Process for preparing tetraalkylammonium salt of 6-halogenopurine derivative |
| WO2002057288A1 (en) * | 2001-01-19 | 2002-07-25 | Lg Life Sciences Ltd. | Novel acyclic nucleoside phosphonate derivatives, salts thereof and process for the preparation of the same |
-
2003
- 2003-12-19 KR KR1020030093942A patent/KR20050062940A/en not_active Application Discontinuation
-
2004
- 2004-12-10 WO PCT/KR2004/003257 patent/WO2005058925A1/en active Application Filing
- 2004-12-10 TW TW93138308A patent/TW200526225A/en unknown
- 2004-12-17 AR ARP040104723A patent/AR046948A1/en not_active Application Discontinuation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5302585A (en) * | 1990-04-20 | 1994-04-12 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Use of chiral 2-(phosphonomethoxy)propyl guanines as antiviral agents |
| US5977089A (en) * | 1996-07-26 | 1999-11-02 | Gilead Sciences, Inc. | Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability |
| EP0967213A1 (en) * | 1998-06-23 | 1999-12-29 | SUMIKA FINE CHEMICALS Co., Ltd. | Process for preparing tetraalkylammonium salt of 6-halogenopurine derivative |
| WO2002057288A1 (en) * | 2001-01-19 | 2002-07-25 | Lg Life Sciences Ltd. | Novel acyclic nucleoside phosphonate derivatives, salts thereof and process for the preparation of the same |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8093229B2 (en) | 2005-03-30 | 2012-01-10 | Conforma Therapeutics Corporation | Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs as HSP90-inhibitors |
| US8710047B2 (en) | 2008-05-29 | 2014-04-29 | Albany Molecular Research, Inc. | 5-HT3 receptor modulators, methods of making, and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20050062940A (en) | 2005-06-28 |
| AR046948A1 (en) | 2006-01-04 |
| TW200526225A (en) | 2005-08-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20090286989A1 (en) | Process for High Purity Anastrozole | |
| WO2005058925A1 (en) | New process for preparing diisopropyl ((1-((2-amino-6-halo-9h-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonate | |
| EP1794140A2 (en) | Process for the preparation of citalopram and escitalopram | |
| US6583285B1 (en) | Process for preparing zolpidem | |
| EP1395586B1 (en) | Method for the production of zolpidem | |
| US7759487B2 (en) | Preparation of ketone amides | |
| KR20190013554A (en) | Novel intermediates useful for the synthesis of aminopyrimidine derivatives, process for preparing the same, and process for preparing aminopyrimidine derivatives using the same | |
| KR20160027536A (en) | Process for preparing an intermediate useful for the synthesis of silodosin | |
| JP2014510698A (en) | Atobacon manufacturing method | |
| JP4345095B2 (en) | Method for highly selective O-alkylation of amide compounds using copper salts | |
| WO2005058926A1 (en) | New process for preparing diisopropyl ((1-((2-amino-6-chloro-9h-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonate | |
| KR101453413B1 (en) | Method for preparation of alpha-carboline derivatives | |
| KR100311949B1 (en) | Process for the preparation of 1-[(cyclopent-3-en-1-yl)methyl]-5-ethyl-6-(3,5-dimethylbenzoyl)-2,4-pyrimidinedione | |
| JP2000229930A (en) | Production of cyanoacetate ester | |
| JP4018816B2 (en) | Cycloheptenone derivative and method for producing the same, and method for producing cycloheptimidazole derivative using the same | |
| CN114573432A (en) | Method for preparing 4-halo-2-trifluoromethylacetophenone | |
| DE10063106A1 (en) | Process for the preparation of 2- (2-ethoxyphenyl) substituted imidazotriazinones | |
| US6300512B1 (en) | Method for producing a 1-(3-cyclopentenyloxy-4-alkoxyphenyl)-4-oxocyclohexanecar-bonitrile | |
| JP3581721B2 (en) | Method for producing N-substituted-3-iodopropioamide and its synthetic intermediate | |
| JP2003104985A (en) | Method for producing quinazoline derivative | |
| KR20210104730A (en) | Isoquinoline sulfonyl chloride acid addition salt and method for preparing the same | |
| CN101010293A (en) | Chiral 3-halophthalic acid derivatives | |
| JP2006001847A (en) | Method for producing 2,5-diamino-4,6-dichloropyrimidine |
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 BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG 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 NA 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): BW GH GM KE LS MW MZ NA 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 IS IT LT LU MC NL PL 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 | ||
| DPEN | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed from 20040101) | ||
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| WWW | Wipo information: withdrawn in national office |
Country of ref document: DE |
|
| 122 | Ep: pct application non-entry in european phase |