AR128049A1 - Proceso de preparación de apalutamida, compuestos intermediarios utilizados en dicho proceso y proceso para la preparación de una dispersión sólida amorfa (dsa) que contiene la apalutamida - Google Patents
Proceso de preparación de apalutamida, compuestos intermediarios utilizados en dicho proceso y proceso para la preparación de una dispersión sólida amorfa (dsa) que contiene la apalutamidaInfo
- Publication number
- AR128049A1 AR128049A1 ARP220103529A ARP220103529A AR128049A1 AR 128049 A1 AR128049 A1 AR 128049A1 AR P220103529 A ARP220103529 A AR P220103529A AR P220103529 A ARP220103529 A AR P220103529A AR 128049 A1 AR128049 A1 AR 128049A1
- Authority
- AR
- Argentina
- Prior art keywords
- formula
- apalutamide
- compound
- preparation
- fluoro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 8
- HJBWBFZLDZWPHF-UHFFFAOYSA-N apalutamide Chemical class C1=C(F)C(C(=O)NC)=CC=C1N1C2(CCC2)C(=O)N(C=2C=C(C(C#N)=NC=2)C(F)(F)F)C1=S HJBWBFZLDZWPHF-UHFFFAOYSA-N 0.000 title abstract 7
- 229950007511 apalutamide Drugs 0.000 title abstract 7
- 238000002360 preparation method Methods 0.000 title abstract 4
- 239000007787 solid Substances 0.000 title abstract 2
- 238000000034 method Methods 0.000 title 2
- 239000006185 dispersion Substances 0.000 title 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract 6
- 239000000543 intermediate Substances 0.000 abstract 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 abstract 2
- 238000004519 manufacturing process Methods 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 abstract 2
- 238000000746 purification Methods 0.000 abstract 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract 2
- FGOGELABKVPEAL-UHFFFAOYSA-N 1-[3-fluoro-4-(methylcarbamoyl)anilino]cyclobutane-1-carboxylic acid Chemical compound C1=C(F)C(C(=O)NC)=CC=C1NC1(C(O)=O)CCC1 FGOGELABKVPEAL-UHFFFAOYSA-N 0.000 abstract 1
- FVTVMQPGKVHSEY-NUTRPMROSA-N 1-aminocyclobutane-1-carboxylic acid Chemical class NC1(CCC1)[11C](=O)O FVTVMQPGKVHSEY-NUTRPMROSA-N 0.000 abstract 1
- WLMSCOVORZUSNW-UHFFFAOYSA-N 5-amino-3-(trifluoromethyl)pyridine-2-carbonitrile Chemical compound NC1=CN=C(C#N)C(C(F)(F)F)=C1 WLMSCOVORZUSNW-UHFFFAOYSA-N 0.000 abstract 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000009833 condensation Methods 0.000 abstract 1
- 230000005494 condensation Effects 0.000 abstract 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 abstract 1
- 230000032050 esterification Effects 0.000 abstract 1
- 238000005886 esterification reaction Methods 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 abstract 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 abstract 1
- 239000007962 solid dispersion Substances 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
-
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dispersion Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La presente invención se refiere al proceso de preparación de Apalutamida, de fórmula (1). Además, se refiere a los intermediarios de síntesis utilizados en el proceso de preparación de la Apalutamida, de fórmula (XI) y de fórmula (XII). También la presente invención comprende un proceso de preparación de la Dispersión Sólida Amorfa que contiene Apalutamida, un excipiente farmacéuticamente aceptable en uno o más solventes seleccionados entre metanol, acetona, o sus mezclas. Reivindicación 1: Un proceso de preparación de apalutamida de fórmula (1) caracterizado porque comprende las siguientes etapas: a. sustitución nucleofílica del ácido 1-aminociclobutano-1-carboxílico haciendo reaccionar el compuesto de fórmula (X-I): 4-halógeno-2-fluoro-N-metilbenzamida en presencia de carbonato de potasio, yoduro cuproso, dimetilsulfoxido y agua, para obtener el compuesto de fórmula (A-1): ácido 1-((3-fluoro-4-(metilcarbamoil)fenil)amino)ciclobutano-1-carboxílico; b. purificación por recristalización del compuesto A-1 empleando el sólido húmedo o seco; c. esterificación del compuesto obtenido en el paso (a) o (b) para dar un compuesto de fórmula (A-2): 1-((3-fluoro-4-(metillcarbamoil)fenil)amino)ciclobutano-1-carboxilato de metilo, en presencia de metanol y cloruro de tionilo; d. hacer reaccionar un compuesto de fórmula (II): 5-amino-3-(trifluorometil)picolinonitrilo con un agente tiocarbonilante para obtener un compuesto intermediario de fórmula (XI); e. condensación del intermediario de fórmula (XI) o (XII) o su mezcla con un éster de fórmula (A-2) del paso b) para obtener apalutamida cruda de fórmula (1); y f. purificación del producto del paso d.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CL2021/050136 WO2023122842A1 (es) | 2021-12-31 | 2021-12-31 | Proceso para la preparación de apalutamida, intermediarios de sintesis y la dispersion solida amorfa que la contiene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR128049A1 true AR128049A1 (es) | 2024-03-20 |
Family
ID=86996733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP220103529A AR128049A1 (es) | 2021-12-31 | 2022-12-21 | Proceso de preparación de apalutamida, compuestos intermediarios utilizados en dicho proceso y proceso para la preparación de una dispersión sólida amorfa (dsa) que contiene la apalutamida |
Country Status (2)
| Country | Link |
|---|---|
| AR (1) | AR128049A1 (es) |
| WO (1) | WO2023122842A1 (es) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MA41107A (fr) * | 2014-12-05 | 2017-10-10 | Aragon Pharmaceuticals Inc | Compositions anti-cancéreuses |
| CN108069869B (zh) * | 2016-11-09 | 2022-03-01 | 上海医药工业研究院 | 一种Apalutamide的制备方法及其中间体 |
| TW201831461A (zh) * | 2017-01-18 | 2018-09-01 | 台灣神隆股份有限公司 | 製備阿帕魯醯胺的方法 |
| IN202041007966A (es) * | 2020-02-25 | 2021-08-27 |
-
2021
- 2021-12-31 WO PCT/CL2021/050136 patent/WO2023122842A1/es unknown
-
2022
- 2022-12-21 AR ARP220103529A patent/AR128049A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2023122842A1 (es) | 2023-07-06 |
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