ES2585221T3 - Un proceso para la preparación de 6-(7-((1-aminociclopropil)metoxi)-6-metoxiquinolin-4-iloxi)-n-metil-1-naftamida y productos intermedios sintéticos de la misma - Google Patents
Un proceso para la preparación de 6-(7-((1-aminociclopropil)metoxi)-6-metoxiquinolin-4-iloxi)-n-metil-1-naftamida y productos intermedios sintéticos de la misma Download PDFInfo
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- ES2585221T3 ES2585221T3 ES13172499.9T ES13172499T ES2585221T3 ES 2585221 T3 ES2585221 T3 ES 2585221T3 ES 13172499 T ES13172499 T ES 13172499T ES 2585221 T3 ES2585221 T3 ES 2585221T3
- Authority
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- Prior art keywords
- methyl
- methoxy
- aminocyclopropyl
- methoxyquinolin
- yloxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000002360 preparation method Methods 0.000 title description 3
- CUDVHEFYRIWYQD-UHFFFAOYSA-N E-3810 free base Chemical compound C=1C=C2C(C(=O)NC)=CC=CC2=CC=1OC(C1=CC=2OC)=CC=NC1=CC=2OCC1(N)CC1 CUDVHEFYRIWYQD-UHFFFAOYSA-N 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- -1 p-toluenesulfonyl Chemical group 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 abstract 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 abstract 1
- 125000005544 phthalimido group Chemical group 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 abstract 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 abstract 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- VAZQQRNYILEOGE-UHFFFAOYSA-N benzyl n-[1-(hydroxymethyl)cyclopropyl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC1(CO)CC1 VAZQQRNYILEOGE-UHFFFAOYSA-N 0.000 description 2
- GPPHNOAJKPDJAA-UHFFFAOYSA-N benzyl n-[1-[(4-acetyl-2-methoxy-5-nitrophenoxy)methyl]cyclopropyl]carbamate Chemical compound COC1=CC(C(C)=O)=C([N+]([O-])=O)C=C1OCC1(NC(=O)OCC=2C=CC=CC=2)CC1 GPPHNOAJKPDJAA-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DFYRUELUNQRZTB-UHFFFAOYSA-N apocynin Chemical compound COC1=CC(C(C)=O)=CC=C1O DFYRUELUNQRZTB-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- SXLBULLJGDJVCF-UHFFFAOYSA-N benzyl n-[1-[[4-[3-(dimethylamino)prop-2-enoyl]-2-methoxy-5-nitrophenoxy]methyl]cyclopropyl]carbamate Chemical compound COC1=CC(C(=O)C=CN(C)C)=C([N+]([O-])=O)C=C1OCC1(NC(=O)OCC=2C=CC=CC=2)CC1 SXLBULLJGDJVCF-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- XEWZVRYIPAYMLS-UHFFFAOYSA-N tert-butyl n-[1-[(4-acetyl-2-methoxy-5-nitrophenoxy)methyl]cyclopropyl]carbamate Chemical compound COC1=CC(C(C)=O)=C([N+]([O-])=O)C=C1OCC1(NC(=O)OC(C)(C)C)CC1 XEWZVRYIPAYMLS-UHFFFAOYSA-N 0.000 description 1
- QGKJNNYJHBEIQQ-UHFFFAOYSA-N tert-butyl n-[1-[(4-acetyl-2-methoxyphenoxy)methyl]cyclopropyl]carbamate Chemical compound COC1=CC(C(C)=O)=CC=C1OCC1(NC(=O)OC(C)(C)C)CC1 QGKJNNYJHBEIQQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/44—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/24—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Un compuesto de formula (XI) o (XIa):**Fórmula** en donde R' es hidrógeno y R se selecciona de bencilo, acetilo, benzoilo, trifluorometanosulfonilo, bencenosulfonilo, p-toluenosulfonilo, metoxicarbonilo, etoxicarbonilo, tert-butoxicarbonilo, aliloxicarbonilo y benciloxicarbonilo opcionalmente sustituido en el anillo aromático con hasta tres sustituyentes seleccionados de halógeno, ciano y trifluorometilo; o R' es trimetilsililo y R es tert-butoxicarbonilo; o R y R' tomados junto con el átomo de nitrógeno al que están enlazados forman un grupo ftalimido.
Description
5
Un reactor de 10 l equipado con un agitador mecánico se cargó con trifenilfosfina (340.0 g, 1.296 mol) y THF (2 l) y la suspensión se enfrió en un baño helado. La suspensión agitada se añadió después lentamente con DIAD (264 g,
1.296 mol) durante 30 minutos. Después de agitar por 30 min a 0°C, la suspensión agitada se añadió en forma de gotas con una solución de 4-hidroxi-3-metoxiacetofenona (180 g, 1.08 mol) y DIPEA (210 g, 1.62 mol) en THF (1500 10 ml). La suspensión se dejó bajo agitación por 45 min a 0°C, después se añadió en forma de gotas con una solución de 1-benciloxicarbonilamino-1-hidroximetilciclopropano (China Gateway) (240 g, 1.08 mol) en THF (1500 ml). Después de 1h, el análisis LC-MS de una muestra de la mezcla de reacción mostró la desaparición completa de 1benciloxicarbonilamino-1-hidroximetilciclopropano. La mezcla de reacción se evaporó y el producto crudo se recristalizó con EtOH 95% (4000 ml) para dar 1-[(4-acetil-2-metoxifenoxi)metil]-N-benciloxicarbonil-1
15 aminociclopropano (214 g, rendimiento: 53.5%) como un sólido blanco. 1H-RMN (300 MHz, CDCl3): δ: 7.41-7.45 (m, 2 H), 7.26 (s, 5 H), 6.77 (d, 1 H), 5.43 (s, 1H), 5.00 (s, 2 H), 4.04 (s, 2 H), 3.82 (s, 3 H), 2.49 (s, 3H), 0.92 (m, 4 H). LC-MS: M+H+: 370.4
20 Los siguientes compuestos se prepararon análogamente:
1-[(4-Acetil-2-metoxifenoxi)metil)-N-etoxicarbonil-1-aminociclopropano; 1-[(4-Acetil-2-metoxifenoxi)metil]-N-tert-butoxicarbonil-1-aminociclopropano.
25 Ejemplo 2: Preparación de 1-[(4-acetil-2-metoxi-5-nitrofenoxi)metil]-N-benciloxicarbonil-1-aminociclopropano
Una solución de HNO3 (65%, 3 ml) en Ac2O (2 ml) a 0°C se añadió lentamente con una suspensión del compuesto
30 del Ejemplo 1 (1.1 g, 2.9 mmol) en Ac2O (3 ml). Después de agitar a 0°C por 2 h, la mezcla de reacción se vertió en 50 ml de hielo/agua y el precipitado se recuperó por filtración. El sólido amarillo resultante se recristalizó con 95% EtOH (5 ml) para dar 1-[(4-acetil-2-metoxi-5-nitrofenoxi)metil]-N-benciloxicarbonil-1-aminociclopropano (0.69 g, rendimiento: 56%) como un sólido amarillo.1H-RMN (300 MHz, CDC]3): δ: 7.52 (s, 1H), 7.26 (s, 5 H), 6.67 (s, 1 H), 5.36 (s, 1H), 5.02 (s, 2 H), 4.05 (s, 2 H), 3.86
35 (s, 3 H), 2.42 (s, 3 H), 0.94 (m, 4 H). LC-MS: M+H+: 414.41
Los siguientes compuestos se prepararon análogamente:
40 1-[(4-Acetil-2-metoxi-5-nitrofenoxi)metil]-N-etoxicarbonil)-1-aminociclopropano; 1-[(4-Acetil-2-metoxi-5-nitrofenoxi)metil]-N-(tert-butoxicarbonil)-1-aminociclopropano.
Ejemplo 3: Preparación de 1-[(4-(3-dimetilaminopropenoil)-2-metoxi-5-nitrofenoxi) metil]-N-benciloxicarbonil-1aminociclopropano
45
9
Una mezcla del compuesto del Ejemplo 6 (0.24 g, 0.42 mmol) en 2 ml de una solución de 40% HBr en ácido acético se agitó a 30°C por 3h, después se añadió con 10 ml de agua y la mezcla de reacción se extrajo con AcOEt (2 x 10 5 ml). Las fases orgánicas se eliminaron. La solución acuosa se añadió en forma de gotas con una solución de 50% NaOH para alcanzar pH 10. La mezcla se extrajo con DCM (3 x 20 ml) y las fases orgánicas combinadas se secaron y se evaporaron para dar un crudo que contiene 6-(7-((1-aminociclopropil)metoxi)-6-metoxiquinolin-4-iloxi)-N-metil-1naftamida (I) con pureza mayor que >94% por análisis LC-MS. Este crudo se purificó después por cromatografía en una columna de gel de sílice eluyendo con DCM/MeOH 10:1), para proporcionar 6-(7-((1-aminociclopropil)metoxi)-6
10 metoxiquinolin-4-iloxi)-N-metil-1-naftamida (I) con pureza mayor que 98% por análisis LC-MS (140 mg, rendimiento: 76%).1H-RMN (500 MHz, DMSO-d6) δ ppm: 8.47 (d, 2 H), 7.87 (d, 1 H), 7.53 (m, 3 H), 7.51 (m, 1 H), 7.44 (d, 1 H), 7.38 (s, 1 H), 6.50 (d, 1 H), 6.16 (d, 1 H), 5.01 (s, 2 H), 4.05 (s, 2 H), 4.03 (s, 3 H), 3.12 (d, 3 H), 2.09 (m, 2 H), 0.80 (m, 4 H). LC-MS: M+H+: 444.0
15
12
Claims (1)
-
imagen1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI2009A000397A IT1393351B1 (it) | 2009-03-16 | 2009-03-16 | Procedimento per la preparazione della 6-(7-((1-amminociclopropil)metossi)-6-metossichinolin-4-ilossi)-n-metil-1-naftammide e suoi intermedi di sintesi |
| ITMI20090397 | 2009-03-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2585221T3 true ES2585221T3 (es) | 2016-10-04 |
Family
ID=41210541
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13172499.9T Active ES2585221T3 (es) | 2009-03-16 | 2010-03-11 | Un proceso para la preparación de 6-(7-((1-aminociclopropil)metoxi)-6-metoxiquinolin-4-iloxi)-n-metil-1-naftamida y productos intermedios sintéticos de la misma |
| ES10712320T Active ES2431618T3 (es) | 2009-03-16 | 2010-03-11 | Un proceso para la preparación de 6-(7-((1-aminociclopropil)metoxi)-6-metoxiquinolin-4-iloxi)-N-metil-1-naftamida y productos intermedios sintéticos de la misma |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10712320T Active ES2431618T3 (es) | 2009-03-16 | 2010-03-11 | Un proceso para la preparación de 6-(7-((1-aminociclopropil)metoxi)-6-metoxiquinolin-4-iloxi)-N-metil-1-naftamida y productos intermedios sintéticos de la misma |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US8642767B2 (es) |
| EP (3) | EP2408739B1 (es) |
| JP (2) | JP5817079B2 (es) |
| CN (3) | CN104193676B (es) |
| CY (2) | CY1114503T1 (es) |
| DK (2) | DK2408739T3 (es) |
| ES (2) | ES2585221T3 (es) |
| HR (2) | HRP20130978T1 (es) |
| HU (1) | HUE029528T2 (es) |
| IT (1) | IT1393351B1 (es) |
| PL (2) | PL2408739T3 (es) |
| PT (2) | PT2408739E (es) |
| SI (2) | SI2641897T1 (es) |
| SM (1) | SMT201600356B (es) |
| WO (1) | WO2010105761A1 (es) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1393351B1 (it) | 2009-03-16 | 2012-04-20 | Eos Ethical Oncology Science Spa In Forma Abbreviata Eos Spa | Procedimento per la preparazione della 6-(7-((1-amminociclopropil)metossi)-6-metossichinolin-4-ilossi)-n-metil-1-naftammide e suoi intermedi di sintesi |
| EP2945931A4 (en) * | 2013-01-18 | 2016-10-12 | Advenchen Pharmaceuticals Llc | PROCESS FOR THE PREPARATION OF ANTITUMOR AGENT, 6- (7 - ((1-AMINO-CYCLO-PROPYL) -METHOXY) -6-METHOXYQUINOLIN-4-YLOXY) -N-METHYL-1-NAPHTHAMIDE, AND His crystalline form |
| CN105311029A (zh) | 2014-06-06 | 2016-02-10 | 正大天晴药业集团股份有限公司 | 抗肿瘤活性的喹啉衍生物 |
| CN105311030B (zh) | 2014-06-06 | 2020-03-24 | 正大天晴药业集团股份有限公司 | 用于抗肿瘤的螺取代化合物 |
| AU2015290007B2 (en) | 2014-07-14 | 2019-11-21 | Advenchen Pharmaceuticals, Nanjing Ltd. | Fused quinoline compunds as pi3k, mTor inhibitors |
| US10307412B2 (en) | 2014-12-09 | 2019-06-04 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Quinoline derivative against non-small cell lung cancer |
| US9751859B2 (en) | 2015-05-04 | 2017-09-05 | Advenchen Pharmaceuticals, LLC | Process for preparing an anti-cancer agent, 1-((4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropanamine, its crystalline form and its salts |
| AU2016293841B2 (en) | 2015-07-11 | 2020-10-08 | Advenchen Pharmaceuticals, LLC | Fused quinoline compunds as pi3k/mTor inhibitors |
| EP3359526A4 (en) | 2015-10-05 | 2019-04-03 | The Trustees of Columbia University in the City of New York | ACTIVATORS OF AUTOPHAGIC RIVER AND PHOSPHOLIPASE D AND PURIFICATION OF PROTEIN AGGREGATES INCLUDING TAU AND TREATMENT OF PROTEINOPATHIES |
| CN107296811B (zh) | 2016-04-15 | 2022-12-30 | 正大天晴药业集团股份有限公司 | 一种用于治疗胃癌的喹啉衍生物 |
| CN109748902B (zh) * | 2017-11-02 | 2020-11-06 | 杭州科巢生物科技有限公司 | 一种盐酸安罗替尼的制备方法 |
| CN111936467B (zh) | 2018-03-02 | 2022-02-18 | 正大天晴药业集团股份有限公司 | 作为c-Met激酶抑制剂的化合物的结晶及其制备方法和用途 |
| AU2019232437A1 (en) | 2018-03-07 | 2020-10-08 | Bayer Aktiengesellschaft | Identification and use of ERK5 inhibitors |
| CN110483393A (zh) * | 2018-05-14 | 2019-11-22 | 上海海和药物研究开发有限公司 | 德立替尼的晶型 |
| CN110483392A (zh) * | 2018-05-14 | 2019-11-22 | 上海海和药物研究开发有限公司 | 合成n-保护的喹啉-7-基氧基甲基环丙基胺衍生物的方法及合成中间体 |
| CN116444489A (zh) * | 2018-12-29 | 2023-07-18 | 正大天晴药业集团股份有限公司 | 喹啉衍生物及其制备方法和用途 |
| CN115160221B (zh) * | 2022-07-26 | 2024-10-18 | 恩祺生物科技(上海)有限公司 | 德立替尼晶型化合物和用途 |
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| CA2273181C (en) * | 1996-12-23 | 2004-01-20 | Hoechst Marion Roussel, Inc. | 3-aryl-2-(1-substituted-4-piperidinyl)-1(1-di)oxo-3h-benzo[d]-isothiazole derivatives, their preparation and their use as modulators of neurotransmitter function |
| BRPI0017548B8 (pt) * | 1999-02-10 | 2023-05-02 | Astrazeneca Ab | Composto |
| AU2003257666A1 (en) * | 2002-08-23 | 2004-03-11 | Kirin Beer Kabushiki Kaisha | COMPOUND HAVING TGFss INHIBITORY ACTIVITY AND MEDICINAL COMPOSITION CONTAINING THE SAME |
| AP2006003619A0 (en) * | 2003-12-23 | 2006-06-30 | Pfizer | Novel quinoline derivatives |
| US8163923B2 (en) | 2007-03-14 | 2012-04-24 | Advenchen Laboratories, Llc | Spiro substituted compounds as angiogenesis inhibitors |
| IT1393351B1 (it) | 2009-03-16 | 2012-04-20 | Eos Ethical Oncology Science Spa In Forma Abbreviata Eos Spa | Procedimento per la preparazione della 6-(7-((1-amminociclopropil)metossi)-6-metossichinolin-4-ilossi)-n-metil-1-naftammide e suoi intermedi di sintesi |
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