ES2562981T3 - Un procedimiento para la preparación de Etoricoxib - Google Patents
Un procedimiento para la preparación de Etoricoxib Download PDFInfo
- Publication number
- ES2562981T3 ES2562981T3 ES10719784.0T ES10719784T ES2562981T3 ES 2562981 T3 ES2562981 T3 ES 2562981T3 ES 10719784 T ES10719784 T ES 10719784T ES 2562981 T3 ES2562981 T3 ES 2562981T3
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- formula
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- etoricoxib
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- iiib
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- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 title abstract description 13
- 229960004945 etoricoxib Drugs 0.000 title abstract description 13
- 238000000034 method Methods 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 10
- 150000001875 compounds Chemical class 0.000 abstract description 9
- -1 chloroacetyl halide Chemical class 0.000 abstract description 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 abstract description 5
- 150000003839 salts Chemical class 0.000 abstract description 4
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 abstract 1
- 229940106681 chloroacetic acid Drugs 0.000 abstract 1
- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Un procedimiento para la preparación de Etoricoxib de fórmula-(I) que comprende,**Fórmula** (a) hacer reaccionar un compuesto de fórmula (IV) con un haluro de cloroacetilo adecuado o ácido cloroacético y oxicloruro fosforoso para obtener el compuesto de fórmula (IIId) y convertir adicionalmente el compuesto de fórmula (IIId) en su sal adecuada para obtener el compuesto de fórmula-(IIIb),**Fórmula** en donde representa un grupo cíclico, que contiene opcionalmente uno o más heteroátomos seleccionados entre N, O S y 'X-' representa un contraión adecuado. (b) hacer reaccionar el compuesto de fórmula (IIIb) con un compuesto de fórmula (II) en presencia de una base adecuada y un disolvente adecuado para obtener el Etoricoxib de fórmula (I) **Fórmula**
Description
Preferiblemente, los grupos que comprenden
5 se pueden seleccionar entre un grupo morfolidinilo, piperidinilo y pirrolidinilo.
Preferiblemente, la etapa (a) comprende adicionalmente la preparación de un compuesto de fórmula (IIIb) como se ha descrito anteriormente.
10 Preferiblemente, la sal de β-clorovinamidinio de fórmula (IIIb) es la descrita anteriormente. Preferiblemente, la etapa (a) comprende combinar en primer lugar cloruro de cloroacetilo y oxicloruro de fósforo, y después de eso combinar el compuesto de N-formilo de fórmula (IV), para obtener la sal de β-clorovinamidinio de fórmula (IIIb), mediante los procedimientos descritos anteriormente. Preferiblemente, la temperatura en la etapa (a) es la
15 descrita anteriormente.
Preferiblemente, la mezcla de reacción se mantiene en la etapa (a) como se ha descrito anteriormente. Antes de la etapa (b), se separa la sal de β-clorovinamidinio de fórmula (IIIb) obtenida en la etapa (a). Preferiblemente, la separación se realiza mediante filtración como se ha descrito antes en la memoria descriptiva.
20 El disolvente orgánico de la etapa (b) se puede seleccionar del grupo que comprende hidrocarburos adecuados tales como benceno, tolueno, xileno, etilbenceno, trimetilbenceno y similares; disolventes hidrocarbonados halogenados adecuados tales como cloroformo, diclorometano, dicloroetano y similares o mezclas de los mismos; alcoholes tales como metanol, etanol, t-butanol y similares o mezclas de los mismos; cetonas tales
25 como acetona; disolventes apróticos tales como DMF, dimetilacetamida; éteres como éter dietílico, 1,4-dioxano, DIPE, MTBE, THF y similares, disolventes polares apróticos tales como DMF, DMSO, DMA; nitrilos como acetonitrilo o sus mezclas adecuadas.
La base adecuada utilizada en la etapa (b) se puede seleccionar entre las bases orgánicas o inorgánicas
30 adecuadas tales como hidróxidos seleccionados entre NaOH, KOH y similares, carbonatos tales como NaHCO3, Na2CO3, K2CO3, hidruros tales como NaH y LHMDS, KHMDS y similares; alcóxidos de metales alcalinos tales como t-butóxido de sodio, potasio, litio y similares; isopropóxido de sodio, potasio, litio y similares.
Opcionalmente, una vez completada la etapa (b) el compuesto de fórmula (I) se puede aislar o someter a
35 purificación en situ. La purificación del compuesto de fórmula (I) se puede realizar utilizando una disolución de formalina y amoníaco acuoso en un disolvente adecuado. La mezcla de reacción se agita a una temperatura adecuada y el producto se aísla utilizando un disolvente adecuado. A continuación se lleva a cabo la recristalización utilizando un disolvente adecuado para obtener Etoricoxib puro.
10
El disolvente adecuado utilizado para la purificación de Etoricoxib se puede seleccionar a partir de un alcohol C1-C5 ; cetonas tales como acetona y metil etil cetona; éteres tales como THF y dioxano o sus mezclas adecuadas.
El disolvente adecuado utilizado para el aislamiento de Etoricoxib se puede seleccionar entre alcoholes o ésteres 5 adecuados. El disolvente preferido es alcohol isopropílico.
El disolvente adecuado utilizado para la recristalización de Etoricoxib se puede seleccionar entre alcoholes, ésteres, éteres adecuados o sus mezclas adecuadas. El disolvente preferido para la recristalización es el alcohol isopropílico.
10 [0069] En una de las realizaciones de la invención se describe Etoricoxib obtenido de acuerdo con el procedimiento de la presente invención con una pureza de al menos 99,9 % mediante HPLC.
El Etoricoxib obtenido de acuerdo con el procedimiento de la presente invención se caracteriza por un patrón de 15 XPRD sustancialmente de acuerdo con el patrón de la Fig. 1.
El Etoricoxib obtenido de acuerdo con la presente invención también se caracteriza por picos de XPRD en aproximadamente de 7,00, 8,50, 9,67, 11,72, 12,35, 12,96, 13,24, 15,04, 15,44, 16,51, 17,06, 17,70, 18,07, 18,76, 19,34, 20,00, 20,24, 21,14, 21,50, 22,20, 22,70, 23,28, 24,02, 24,76, 25,73, 26,20, 26,90, 27,37, 28,44,
[0072] En una de las realizaciones de la presente invención se describe un intermedio novedoso de fórmula (IIIc), y el uso de este intermedio en el procedimiento de preparación de Etoricoxib. 25
[0073] La sal hexafluorofosfato de 2-cloro 1,3-(bis pirolidinil) trimetinio se aisló y se caracterizó mediante los siguientes datos:
30 RMN H1 (300MHz, DMSO-D6) (ppm): 1,82 -1,95 (8 H, dd), 3,73 (4H, s), 4,01 (4H, s), 7,98 (2H, s); RMN C13 (75MHz, DMSO-D6) (ppm): 23,14, 25,50, 49,51, 56,73, 92,70, 156,53 ESI MS = 212,9 m/z (pico base).
35 [0074] En una realización adicional de la invención se describe una composición farmacéutica de Etoricoxib con un portador líquido o sólido, excipientes como es conocido en la técnica en donde el Etoricoxib es producido mediante el procedimiento descrito anteriormente. La invención se describe adicionalmente mediante los siguientes ejemplos, que se proporcionan solo como ilustración y no se debe interpretar que limitan el alcance de la invención.
40 Ejemplo 1
Preparación de hexafluorofosfato de 2-cloro-1,3-(bismorfolinil)trimetinio
45 Se añadió oxicloruro de fósforo (6,6 g) a N-formilmorfolina (5 g) de -5 a 10°C y con posterioridad se añadió cloruro de cloroacetilo (5 g) a temperatura ambiente y la mezcla de reacción se agitó. Adicionalmente, se añadió N-formilmorfolina (5 g) a la mezcla de reacción a temperatura ambiente y la masa de reacción se calentó a 55110°C durante 3 a 24 horas. La mezcla de reacción se enfrió a continuación a temperatura ambiente para obtener una masa semisólida, que se disolvió en diclorometano y con posterioridad se añadió una solución de
50 Napf6 a 0-10°C a lo largo de un período de una hora. A continuación se añadieron 50 ml de agua, la capa orgánica se separó, se secó y se concentró hasta sequedad a menos de 50°C, para proporcionar hexafluorofosfato de 2-cloro-1,3-(bismorfolinil)trimetinio. Rendimiento = (4 g). Pureza mediante HPLC = 44,63%.
11
Claims (1)
-
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN441MU2009 | 2009-02-27 | ||
| INMU04412009 | 2009-02-27 | ||
| PCT/IN2010/000045 WO2010097802A2 (en) | 2009-02-27 | 2010-01-25 | A process for the preparation of etoricoxib |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2562981T3 true ES2562981T3 (es) | 2016-03-09 |
Family
ID=42290121
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12162558.6T Active ES2496465T3 (es) | 2009-02-27 | 2010-01-25 | Un procedimiento para la preparación de Etoricoxib |
| ES10719784.0T Active ES2562981T3 (es) | 2009-02-27 | 2010-01-25 | Un procedimiento para la preparación de Etoricoxib |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12162558.6T Active ES2496465T3 (es) | 2009-02-27 | 2010-01-25 | Un procedimiento para la preparación de Etoricoxib |
Country Status (10)
| Country | Link |
|---|---|
| EP (2) | EP2401253B1 (es) |
| AR (1) | AR075441A1 (es) |
| BR (1) | BRPI1006374A2 (es) |
| DK (2) | DK2401253T3 (es) |
| ES (2) | ES2496465T3 (es) |
| HU (1) | HUE028730T2 (es) |
| MY (1) | MY163020A (es) |
| PL (2) | PL2479166T3 (es) |
| PT (1) | PT2479166E (es) |
| WO (1) | WO2010097802A2 (es) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112013012008B1 (pt) | 2010-11-15 | 2021-10-13 | Virdev Intermediates Pvt. Ltd | Processo para o inibidor seletivo da ciclo-oxigenase-2 |
| EA023286B1 (ru) | 2011-05-27 | 2016-05-31 | ФАРМА ДжРС, Д.О.О. | Способ получения полиморфной формы i эторикоксиба |
| EP2773618A1 (en) | 2011-11-03 | 2014-09-10 | Cadila Healthcare Limited | An improved process for the preparation of etoricoxib and polymorphs thereof |
| GR1007973B (el) * | 2012-06-26 | 2013-09-12 | Φαρματεν Αβεε, | Νεα ν-οξοιμινο παραγωγα ως ενδιαμεσα μιας βελτιωμενης μεθοδου παρασκευης 2,3-διαρυλο-5-υποκατεστημενων πυριδινων |
| WO2014114352A1 (en) * | 2013-01-25 | 2014-07-31 | Synthon Bv | Process for making etoricoxib |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5593994A (en) | 1994-09-29 | 1997-01-14 | The Dupont Merck Pharmaceutical Company | Prostaglandin synthase inhibitors |
| US5739166A (en) | 1994-11-29 | 1998-04-14 | G.D. Searle & Co. | Substituted terphenyl compounds for the treatment of inflammation |
| US5861419A (en) | 1996-07-18 | 1999-01-19 | Merck Frosst Canad, Inc. | Substituted pyridines as selective cyclooxygenase-2 inhibitors |
| IL127441A (en) | 1996-07-18 | 2003-02-12 | Merck Frosst Canada Inc | Substituted pyridines, pharmaceutical compositions comprising them and their use in the preparation of anti-inflammatory medicaments or as selective cyclooxygenase-2 inhibitors |
| RS49945B (sr) | 1998-04-24 | 2008-09-29 | Merck & Co.Inc., | Postupak za sintetizovanje inhibitora cox-2 |
| JP4425514B2 (ja) | 1999-11-29 | 2010-03-03 | メルク フロスト カナダ リミテツド | ５−クロロ−３−（４−メタンスルホニルフェニル）−６′−メチル−［２，３′］ビピリジニルの多形型、非晶質型および水和型 |
| US6521642B2 (en) | 2000-05-26 | 2003-02-18 | Merck & Co., Inc. | 5-chloro-3-(4-methanesulfonylphenyl)-6′-methyl-[2,3′]bipyridinyl in pure crystalline form and process for synthesis |
| PH12001001175B1 (en) | 2000-05-26 | 2006-08-10 | Merck Sharp & Dohme | 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl- (2,3')bipyridinyl in pure crystalline form and process for synthesis |
| JP2003160563A (ja) * | 2001-11-29 | 2003-06-03 | Sankio Chemical Co Ltd | 新規な３−アミノ−２−プロペニリデンアンモニウム誘導体・ｂｆ４塩 |
| WO2005085199A1 (en) | 2004-01-14 | 2005-09-15 | Cadila Healthcare Limited | Novel polymorphs of etoricoxib |
-
2010
- 2010-01-25 PL PL12162558T patent/PL2479166T3/pl unknown
- 2010-01-25 HU HUE10719784A patent/HUE028730T2/en unknown
- 2010-01-25 DK DK10719784.0T patent/DK2401253T3/en active
- 2010-01-25 DK DK12162558.6T patent/DK2479166T3/da active
- 2010-01-25 MY MYPI2011003123A patent/MY163020A/en unknown
- 2010-01-25 ES ES12162558.6T patent/ES2496465T3/es active Active
- 2010-01-25 BR BRPI1006374A patent/BRPI1006374A2/pt not_active IP Right Cessation
- 2010-01-25 PT PT121625586T patent/PT2479166E/pt unknown
- 2010-01-25 PL PL10719784T patent/PL2401253T3/pl unknown
- 2010-01-25 ES ES10719784.0T patent/ES2562981T3/es active Active
- 2010-01-25 EP EP10719784.0A patent/EP2401253B1/en active Active
- 2010-01-25 WO PCT/IN2010/000045 patent/WO2010097802A2/en not_active Ceased
- 2010-01-25 EP EP12162558.6A patent/EP2479166B1/en not_active Not-in-force
- 2010-02-16 AR ARP100100449A patent/AR075441A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUE028730T2 (en) | 2017-01-30 |
| BRPI1006374A2 (pt) | 2019-09-24 |
| ES2496465T3 (es) | 2014-09-19 |
| EP2479166A1 (en) | 2012-07-25 |
| WO2010097802A3 (en) | 2010-12-23 |
| EP2401253B1 (en) | 2016-01-13 |
| EP2401253A2 (en) | 2012-01-04 |
| DK2401253T3 (en) | 2016-04-18 |
| AR075441A1 (es) | 2011-03-30 |
| MY163020A (en) | 2017-07-31 |
| WO2010097802A2 (en) | 2010-09-02 |
| DK2479166T3 (da) | 2014-09-01 |
| EP2479166B1 (en) | 2014-08-20 |
| PL2479166T3 (pl) | 2014-11-28 |
| PT2479166E (pt) | 2014-11-28 |
| PL2401253T3 (pl) | 2016-05-31 |
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