PE20070315A1 - PROCEDURE FOR THE PREPARATION OF GEMCITABIN - Google Patents
PROCEDURE FOR THE PREPARATION OF GEMCITABINInfo
- Publication number
- PE20070315A1 PE20070315A1 PE2006000283A PE2006000283A PE20070315A1 PE 20070315 A1 PE20070315 A1 PE 20070315A1 PE 2006000283 A PE2006000283 A PE 2006000283A PE 2006000283 A PE2006000283 A PE 2006000283A PE 20070315 A1 PE20070315 A1 PE 20070315A1
- Authority
- PE
- Peru
- Prior art keywords
- compound
- formula
- reaction
- reacting
- given
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract 3
- 239000002904 solvent Substances 0.000 abstract 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 2
- 150000002596 lactones Chemical class 0.000 abstract 2
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 abstract 1
- IJCKBIINTQEGLY-UHFFFAOYSA-N N(4)-acetylcytosine Chemical compound CC(=O)NC1=CC=NC(=O)N1 IJCKBIINTQEGLY-UHFFFAOYSA-N 0.000 abstract 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 1
- 230000001476 alcoholic effect Effects 0.000 abstract 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 abstract 1
- 150000001412 amines Chemical class 0.000 abstract 1
- 150000001720 carbohydrates Chemical class 0.000 abstract 1
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 238000004440 column chromatography Methods 0.000 abstract 1
- 239000012351 deprotecting agent Substances 0.000 abstract 1
- 229930195733 hydrocarbon Natural products 0.000 abstract 1
- 150000002430 hydrocarbons Chemical class 0.000 abstract 1
- 239000012442 inert solvent Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 abstract 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract 1
- YXFVVABEGXRONW-CNRUNOGKSA-N tritiomethylbenzene Chemical compound [3H]CC1=CC=CC=C1 YXFVVABEGXRONW-CNRUNOGKSA-N 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
SE REFIERE A UN PROCEDIMIENTO DE PREPARACION DE GEMCITABINA QUE COMPRENDE: A) HACER REACCIONAR UNA LACTONA DE FORMULA (II) CON UN COMPUESTO DE SILILO (R)3Si-Cl EN PRESENCIA DE UNA BASE TAL COMO IMIDAZOL PARA OBTENER UNA LACTONA PROTEGIDA DE FORMULA (IV), DONDE R ES ALQUILO(C1-C6) O FENILO OPCIONALMENTE SUSTITUIDO, ESTA REACCION SE DA EN UN SOLVENTE INERTE TAL COMO TOLUENO, Y A UNA TEMPERATURA DE -25ºC A 100ºC; B) REDUCIR EL COMPUESTO (IV) CON UN AGENTE REDUCTOR COMO HIDRURO DE DIISOBUTIL ALUMINIO PARA OBTENER UN CARBOHIDRATO PROTEGIDO DE FORMULA (V), DICHA REACCION SE DA EN UN SOLVENTE TAL COMO TOLUENO O DIETIL ETER, Y A UNA TEMPERATURA DE -100ºC A -20ºC; C) REACCIONAR EL COMPUESTO (V) CON R1-X EN PRESENCIA DE UNA BASE TAL COMO TRIETIL AMINA PARA OBTENER EL COMPUESTO DE FORMULA (VII), DONDE X ES HALO Y R1 ES ALQUILSULFONILO(C1-C6) O FENILSULFONILO OPCIONALMENTE SUSTITUIDO, DICHA REACCION SE DA EN UN SOLVENTE DE HIDROCARBUROS TAL COMO CLORURO DE METILENO; D) REACCIONAR EL COMPUESTO (VII) CON EL COMPUESTO (X) TAL COMO N-ACETIL CITOSINA, ENTRE OTROS, PARA OBTENER UN COMPUESTO DE CITIDINA DE FORMULA (VIII), DONDE P1 ES UN GRUPO PROTEGIDO POR SILILO Y P2 ES H O ACILO; E) DESPROTEGER EL COMPUESTO (VIII) UTILIZANDO AGENTES DESPROTECTORES PARA OBTENER UNA MEZCLA DE ISOMEROS DEL COMPUESTO DE FORMULA (IX), DICHA REACCION SE DA EN SOLVENTES ALCOHOLICOS, TETRAHIDROFURANO, ENTRE OTROS; Y F) SEPARAR UN ISOMERO DEL COMPUESTO (IX) MEDIANTE CROMATOGRAFIA EN COLUMNA PARA OBTENER GEMCITABINAIT REFERS TO A PROCEDURE FOR THE PREPARATION OF GEMCITABIN THAT INCLUDES: A) REACTING A LACTONE OF FORMULA (II) WITH A COMPOUND OF SILILO (R) 3Si-Cl IN THE PRESENCE OF A BASE SUCH AS IMIDAZOLE TO OBTAIN A LACTONE PROTECTED FROM FORMULA ( IV), WHERE R IS ALKYL (C1-C6) OR OPTIONALLY SUBSTITUTED PHENYL, THIS REACTION IS GIVEN IN AN INERT SOLVENT SUCH AS TOLUENE, AND AT A TEMPERATURE OF -25ºC TO 100ºC; B) REDUCE THE COMPOUND (IV) WITH A REDUCING AGENT SUCH AS DIISOBUTIL ALUMINUM HYDRIDE TO OBTAIN A PROTECTED CARBOHYDRATE OF FORMULA (V), SAID REACTION IS GIVEN IN A SOLVENT SUCH AS TOLUENE OR DIETHYL ETHER, AND AT A TEMPERATURE OF -100ºC - 20 ° C; C) REACTING THE COMPOUND (V) WITH R1-X IN THE PRESENCE OF A BASE SUCH AS TRIETIL AMINE TO OBTAIN THE COMPOUND OF FORMULA (VII), WHERE X IS HALO AND R1 IS ALKYLSULFONILO (C1-C6) OR FENYLSULFONILO OPTIONALLY SUBSTITUTE REACTION OCCURS IN A HYDROCARBON SOLVENT SUCH AS METHYLENE CHLORIDE; D) REACTING THE COMPOUND (VII) WITH THE COMPOUND (X) SUCH AS N-ACETYL CYTOSINE, AMONG OTHERS, TO OBTAIN A CITIDINE COMPOUND OF FORMULA (VIII), WHERE P1 IS A PROTECTED GROUP BY SILIL AND P2 IS H OR ACILO; E) UNPROTECTING THE COMPOUND (VIII) USING DEPROTECTING AGENTS TO OBTAIN A MIXTURE OF ISOMERS FROM THE COMPOUND OF FORMULA (IX), SAID REACTION IS GIVEN IN ALCOHOLIC SOLVENTS, TETRAHYDROFURAN, AMONG OTHERS; AND F) SEPARATE AN ISOMER FROM THE COMPOUND (IX) THROUGH COLUMN CHROMATOGRAPHY TO OBTAIN GEMCITABIN
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2005/000256 WO2007015257A2 (en) | 2005-08-04 | 2005-08-04 | A process for the preparation of gemcitabine using novel intermediates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20070315A1 true PE20070315A1 (en) | 2007-06-06 |
Family
ID=37600974
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2006000283A PE20070315A1 (en) | 2005-08-04 | 2006-03-14 | PROCEDURE FOR THE PREPARATION OF GEMCITABIN |
Country Status (3)
| Country | Link |
|---|---|
| AR (1) | AR051374A1 (en) |
| PE (1) | PE20070315A1 (en) |
| WO (1) | WO2007015257A2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2007235210A1 (en) * | 2006-02-06 | 2007-10-18 | Dr. Reddy's Laboratories Ltd. | Preparation of gemcitabine |
| CN102659884B (en) * | 2012-04-23 | 2014-07-02 | 南京臣功制药股份有限公司 | Gemcitabine hydrochloride purifying method |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4526988A (en) * | 1983-03-10 | 1985-07-02 | Eli Lilly And Company | Difluoro antivirals and intermediate therefor |
| WO2004041203A2 (en) * | 2002-11-04 | 2004-05-21 | Xenoport, Inc. | Gemcitabine prodrugs, pharmaceutical compositions and uses thereof |
-
2005
- 2005-08-04 WO PCT/IN2005/000256 patent/WO2007015257A2/en not_active Ceased
- 2005-09-21 AR ARP050103954A patent/AR051374A1/en unknown
-
2006
- 2006-03-14 PE PE2006000283A patent/PE20070315A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007015257A2 (en) | 2007-02-08 |
| AR051374A1 (en) | 2007-01-10 |
| WO2007015257A3 (en) | 2008-04-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FC | Refusal |