WO2016151451A1 - A process for the preparation of lorcaserin hydrochloride - Google Patents
A process for the preparation of lorcaserin hydrochloride Download PDFInfo
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- WO2016151451A1 WO2016151451A1 PCT/IB2016/051535 IB2016051535W WO2016151451A1 WO 2016151451 A1 WO2016151451 A1 WO 2016151451A1 IB 2016051535 W IB2016051535 W IB 2016051535W WO 2016151451 A1 WO2016151451 A1 WO 2016151451A1
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- acetate
- lorcaserin
- methyl
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- solvent
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Definitions
- the present invention relates to a process for the preparation of Lorcaserin hydrochloride hemih drate of Formula la,
- Lorcaserin of Formula (I) is chemically known as (R)-8-chIorol-methyl-2,3,4,5- tetrahydro-lH-3-benzazepine hydrochloride.
- Lorcaserin hydrochloride of Formula (I) is an agonist of the 5-HT 2C receptor and shows effectiveness at reducing obesity in animal models and humans. Further, 5-HT 2C receptor is recognized as a well-accepted receptor target for the treatment of obesity, psychiatric, and other disorders.
- Lorcaserin hydrochloride of Formula (I) is approved as anti-obesity agent and is marketed under the brand name Belvi in USA.
- US patent No. 6,953,787 discloses Lorcaserin or a pharmaceutically acceptable salt, solvate or hydrate thereof. US '787 also discloses the process for the preparation of Lorcaserin or a pharmaceutically acceptable salt comprising the step of deprotecting N- trifluoroacetyl-8-chloro- 1 -methyl-2,3 ,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt to form Lorcaserin or a pharmaceutically acceptable salt.
- US 8,168,624 disclose crystalline forms of Lorcaserin hydrochloride, namely three crystalline forms of Lorcaserin hydrochloride, individually designated as Form I, Form II and Form III (hemihydrate) of Lorcaserin hydrochloride.
- Form I and Form II of Lorcaserin hydrochloride are anhydrous, hygroscopic forms, both of which readily convert to Form III (hemihydrate) of Lorcaserin hydrochloride of Formula (la), upon exposure to moisture.
- US '624 also discloses a process for the preparation of Lorcaserin hydrochloride hemihydrate of Formula (la) which comprises mixing Lorcaserin hydrochloride of Formula (I) with a crystallizing solvent containing water and inducing precipitation of the Lorcaserin hydrochloride hemihydrate of Formula (la) from the crystallizing solvent.
- US 2013/0158013 discloses a crystalline Form IV of Lorcaserin hydrochloride, is an anhydrous polymorph. Further US '013 disclose that Lorcaserin hydrochloride crystalline Form IV is the most stable of anhydrous polymorphs at ambient temperature.
- US '013 also disclose a process for the preparation of Lorcaserin hydrochloride hemihydrate (Form III), comprising slurrying a first mixture comprising Lorcaserin hydrochloride salt Form IV and a first solvent to form (R) -Lorcaserin HCl hemihydrate (Form III).
- the present invention directed towards a process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la) with high purity and high yield,
- the main objective of the present invention is to provide a simple and cost-effective process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la) with high purity and good yield on commercial scale.
- the present invention provides a process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la), which comprises,
- solvent used in step-(i) comprises from ester, halogenated hydrocarbon, ketone, aromatic hydrocarbon or mixture thereof.
- ester comprises from ethyl acetate, n- propyl acetate, n-butyi acetate, isobutyl acetate, t-butyl acetate, methyl acetate or mixtures thereof;
- halogenated hydrocarbon comprises from dichloromethane, 1 ,2-dichloroethane, chloroform, carbon tetrachloride, or mixtures thereof;
- ketone comprises from acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, methyl-pentane-2-one or mixtures thereof;
- aromatic hydrocarbon comprises from toluene, m-xylene, o-xylene, p- xylene or mixtures thereof.
- the process of removing water in step- (ii) from the reaction mixture preferably comprises azeotropic distillation.
- hydrogen chloride gas is passed into the reaction mass or hydrogen chloride in an anhydrous solvent comprises ester or alcohol or mixtures thereof is added to the reaction mass to produce Lorcaserin hydrochloride (I),
- ester comprises from ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate, t-butyl acetate, methyl acetate or mixtures thereof; alcohol comprises from methanol, ethanol, ethylene glycol, 1-propanol, 2- propanol (isopropyl alcohol), 2-methoxyethanol, 1-butanol, 2-butanol or mixtures thereof.
- anti-solvent used in step-(iv) comprises from cyclohexane, pentane, hexane, toluene, cycloheptane, methyl cyclohexane, heptane, or mixture thereof.
- the mixture containing the crystallizing solvent and Lorcaserin hydrochloride is maintained at a temperature of about 40 to about 80, about 50 to about 70, or about 60°C prior to inducing precipitation for a period of about 1 to 24 hours.
- Lorcaserin hydrochloride is dissolved in the crystallizing solvent prior to inducing precipitation.
- the dissolution can be achieved by heating the mixture to a suitable temperature such as between about 40 and about 80° C.
- precipitation of the Lorcaserin hydrochloride heminydrate product can be induced by adding anti solvent, in some embodiments, the mixture is cooled to a temperature of about - 15 to about 15° C. In some embodiments, the mixture is cooled to a temperature of about - 5 to about 10° C. In further embodiments, the mixture is cooled to a temperature of about 0 to about 5° C.
- crystalline Lorcaserin hydrochloride hemihydrate of Formula (la) is isolated by conventional techniques such as filtration and dried the product,
- the present invention provides a compound which is Lorcaserin hydrochloride hemihydrate (la) gains less than about 1.0%, less than about 0.5% or less than about 0.2% weight after undergoing a dynamic vapor sorption cycle.
- Lorcaserin hydrochloride hemihydrate (Form III) shows that it is substantially non-hygroscopic, adsorbing less than 0.5 wt % water at 90% RH and the XRPD pattern showed no change in crystalline form after the dynamic vapor sorption.
- Lorcaserin base which is used as starting material in the present invention can be prepared for example by the procedure disclosed in US 8,367,657.
- Example-1 Process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate:
- Lorcaserin hemitartrate monohydrate salt 100 g was suspended in ethyl acetate (300 mL) and DM water (300mL) at 20-30°C. The above suspension was cooled to 10-15°C. 40% w/w Sodium hydroxide solution (38.13 g) was slowly added for about 30 mins to the reaction mixture at 10-15°C and stirred for 30 minutes. The reaction mass temperature was raised to 20-25°C. Organic layer was separated and the aqueous layer was extracted with ethyl acetate (200 mL). Combined the organic layer and the organic layer was washed with 20% aqueous sodium chloride (400 mL). The solvent from the organic layer was evaporated under reduced pressure at below 40°C to afford oily material.
- the oily material is dissolved in ethyl acetate (100 mL) at 20-30°C.
- the reaction mass was cooled to 0-5°C.
- Ethyl acetate-hydrogen chloride (15% w/w, 101.21 g) was slowly added for about 30 mins to the reaction mixture at 0-5°C.
- n-heptane 400 mL was slowly added for about 30 mins at 0-5°C and stirred for 3 hours at same temperature.
- the reaction mass was filtered and washed with pre-cooled n-heptane (100 mL). The obtained solid was dried at 30-40°C under reduced pressure to afford 75 g of the title compound.
- Lorcaserin hemitartrate monohydrate salt 100 g was suspended in ethyl acetate (200 mL) and DM water (200mL) at 20-30°C. The above suspension was cooled to 10-15°C. 40% w/w Sodium hydroxide solution (38.13 g) was slowly added for about 30 mins to the reaction mixture at 10-15°C and stirred for 30 minutes. The reaction mass temperature was raised to 20-25°C. Organic layer was separated and the aqueous layer was extracted with ethyl acetate (200 mL). Combined the organic layer and the organic layer was washed with 20% aqueous sodium chloride (400 mL). The solvent from the organic layer was evaporated under reduced pressure at below 40°C to afford oily material.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la), which comprises, Formula (la) (i) providing a solution of Lorcaserin base in a solvent; (ii) if water is present, removing water from the reaction mixture; (iii) adding hydrogen chloride to the reaction mixture; (iv) combining the reaction mixture with a suitable anti-solvent; and (v) isolating the crystalline Lorcaserin hydrochloride hemihydrate of Formula (la).
Description
FIELD OF THE INVENTION
The present invention relates to a process for the preparation of Lorcaserin hydrochloride hemih drate of Formula la,
Formula (la)
BACKGROUND OF THE INVENTION
Lorcaserin of Formula (I) is chemically known as (R)-8-chIorol-methyl-2,3,4,5- tetrahydro-lH-3-benzazepine hydrochloride. Lorcaserin hydrochloride of Formula (I) is an agonist of the 5-HT2C receptor and shows effectiveness at reducing obesity in animal models and humans. Further, 5-HT2C receptor is recognized as a well-accepted receptor target for the treatment of obesity, psychiatric, and other disorders. Lorcaserin hydrochloride of Formula (I) is approved as anti-obesity agent and is marketed under the brand name Belvi in USA.
Formula (I)
US patent No. 6,953,787 discloses Lorcaserin or a pharmaceutically acceptable salt, solvate or hydrate thereof. US '787 also discloses the process for the preparation of Lorcaserin or a pharmaceutically acceptable salt comprising the step of deprotecting N- trifluoroacetyl-8-chloro- 1 -methyl-2,3 ,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt to form Lorcaserin or a pharmaceutically acceptable salt.
US 8,168,624 disclose crystalline forms of Lorcaserin hydrochloride, namely three crystalline forms of Lorcaserin hydrochloride, individually designated as Form I, Form II and Form III (hemihydrate) of Lorcaserin hydrochloride. Form I and Form II of Lorcaserin
hydrochloride are anhydrous, hygroscopic forms, both of which readily convert to Form III (hemihydrate) of Lorcaserin hydrochloride of Formula (la), upon exposure to moisture.
US '624 also discloses a process for the preparation of Lorcaserin hydrochloride hemihydrate of Formula (la) which comprises mixing Lorcaserin hydrochloride of Formula (I) with a crystallizing solvent containing water and inducing precipitation of the Lorcaserin hydrochloride hemihydrate of Formula (la) from the crystallizing solvent.
The process is shown in Scheme-I as given below:
US 2013/0158013 discloses a crystalline Form IV of Lorcaserin hydrochloride, is an anhydrous polymorph. Further US '013 disclose that Lorcaserin hydrochloride crystalline Form IV is the most stable of anhydrous polymorphs at ambient temperature.
US '013 also disclose a process for the preparation of Lorcaserin hydrochloride hemihydrate (Form III), comprising slurrying a first mixture comprising Lorcaserin hydrochloride salt Form IV and a first solvent to form (R) -Lorcaserin HCl hemihydrate (Form III).
However, the above processes suffer from low yield and low purity of Lorcaserin HCl hemihydrate (Form III). Therefore, these processes of making Lorcaserin HCl hemihydrate (Form III) are not commercially feasible.
However, there is always a need for an alternative process, which for example, involves use of reagents/solvents that are less expensive and easier to handle, consume smaller amounts of solvents, and provide a higher yield of product with higher purity. Hence, there is a need to develop cost effective and commercially viable process for the preparation of Lorcaserin hydrochloride of Formula (I).
The present invention directed towards a process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la) with high purity and high yield,
OBJECTIVE OF INVENTION
The main objective of the present invention is to provide a simple and cost-effective process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la) with high purity and good yield on commercial scale.
SUMMARY OF THE INVENTION
The present invention provides a process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la), which comprises,
(i) providing a solution of Lorcaserin base in a solvent;
(ii) if water is present, removing water from the reaction mixture;
(iii) adding hydrogen chloride to the reaction mixture;
(iv) combining the reaction mixture with a suitable anti-solvent; and
(v) isolating the crystalline Lorcaserin hydrochloride hemihydrate of Formula (ia).
DETAILED DESCRIPTION OF THE INVENTION
In one embodiment of the present invention provides a process for the preparation of crystalline Lorcaserin h drochloride hemihydrate of Formula (la), which comprises,
(i) providing a solution of Lorcaserin base in a solvent;
(ii) if water is present, removing water from the reaction mixture;
(iii) adding hydrogen chloride to the reaction mixture;
(iv) combining the reaction mixture with a suitable anti-solvent; and
(v) isolating the crystalline Lorcaserin hydrochloride hemihydrate of Formula (la).
In another embodiment of the present invention, solvent used in step-(i) comprises from ester, halogenated hydrocarbon, ketone, aromatic hydrocarbon or mixture thereof.
In another embodiment of the present invention, ester comprises from ethyl acetate, n- propyl acetate, n-butyi acetate, isobutyl acetate, t-butyl acetate, methyl acetate or mixtures thereof; halogenated hydrocarbon comprises from dichloromethane, 1 ,2-dichloroethane, chloroform, carbon tetrachloride, or mixtures thereof; ketone comprises from acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, methyl-pentane-2-one or mixtures thereof; aromatic hydrocarbon comprises from toluene, m-xylene, o-xylene, p- xylene or mixtures thereof.
Yet another embodiment of the present invention, the process of removing water in step- (ii) from the reaction mixture preferably comprises azeotropic distillation. In some embodiment of the present invention, in step-(iii) hydrogen chloride gas is passed into the reaction mass or hydrogen chloride in an anhydrous solvent comprises ester or
alcohol or mixtures thereof is added to the reaction mass to produce Lorcaserin hydrochloride (I),
In some embodiment of the present invention, ester comprises from ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate, t-butyl acetate, methyl acetate or mixtures thereof; alcohol comprises from methanol, ethanol, ethylene glycol, 1-propanol, 2- propanol (isopropyl alcohol), 2-methoxyethanol, 1-butanol, 2-butanol or mixtures thereof.
In another embodiment of the present invention, anti-solvent used in step-(iv) comprises from cyclohexane, pentane, hexane, toluene, cycloheptane, methyl cyclohexane, heptane, or mixture thereof.
In some embodiments, the mixture containing the crystallizing solvent and Lorcaserin hydrochloride is maintained at a temperature of about 40 to about 80, about 50 to about 70, or about 60°C prior to inducing precipitation for a period of about 1 to 24 hours.
In some embodiments, Lorcaserin hydrochloride is dissolved in the crystallizing solvent prior to inducing precipitation. The dissolution can be achieved by heating the mixture to a suitable temperature such as between about 40 and about 80° C. in some embodiments, precipitation of the Lorcaserin hydrochloride heminydrate product can be induced by adding anti solvent, in some embodiments, the mixture is cooled to a temperature of about - 15 to about 15° C. In some embodiments, the mixture is cooled to a temperature of about - 5 to about 10° C. In further embodiments, the mixture is cooled to a temperature of about 0 to about 5° C.
In another embodiment of the present invention, crystalline Lorcaserin hydrochloride hemihydrate of Formula (la) is isolated by conventional techniques such as filtration and dried the product, In some embodiment of the present invention, the present invention provides a compound which is Lorcaserin hydrochloride hemihydrate (la) gains less than about 1.0%, less than about 0.5% or less than about 0.2% weight after undergoing a dynamic vapor sorption cycle. In some embodiment of the present invention, Lorcaserin hydrochloride hemihydrate (Form III) shows that it is substantially non-hygroscopic, adsorbing less than 0.5 wt % water at 90% RH and the XRPD pattern showed no change in crystalline form after the dynamic vapor sorption. In some embodiment of the present invention, Lorcaserin base which is used as starting material in the present invention can be prepared for example by the procedure disclosed in US 8,367,657.
The process disclosed in US '657 involves chlorination of 4~Chlorophenylethyl alcohol to produce 4-Chlorophenylethyl chloride, followed by condensed with l-aminopropan-2-ol to produce l-[(4-chlorophenethyl)amino]propan-2-ol, which is further treated with chlorinating agent to produce 2-Chloro-N-(4-chlorophenethyl)-propan-l -amine. The compound 2-Chloro-N-(4-chlorophenethyl)-propan-l -amine undergoes cyciisation to produce Racemic Lorcaserin, followed by resolution to produce Lorcaserin Base.
The following examples illustrate the nature of the invention and are provided for illustrative purposes only and should not be construed to limit the scope of the invention.
EXAMPLES:
Example-1: Process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate:
Lorcaserin hemitartrate monohydrate salt (100 g) was suspended in ethyl acetate (300 mL) and DM water (300mL) at 20-30°C. The above suspension was cooled to 10-15°C. 40% w/w Sodium hydroxide solution (38.13 g) was slowly added for about 30 mins to the reaction mixture at 10-15°C and stirred for 30 minutes. The reaction mass temperature was raised to 20-25°C. Organic layer was separated and the aqueous layer was extracted with ethyl acetate (200 mL). Combined the organic layer and the organic layer was washed with 20% aqueous sodium chloride (400 mL). The solvent from the organic layer was evaporated under reduced pressure at below 40°C to afford oily material. The oily material is dissolved in ethyl acetate (100 mL) at 20-30°C. The reaction mass was cooled to 0-5°C. Ethyl acetate-hydrogen chloride (15% w/w, 101.21 g) was slowly added for about 30 mins to the reaction mixture at 0-5°C. n-heptane (400 mL) was slowly added for about 30 mins at 0-5°C and stirred for 3 hours at same temperature. The reaction mass was filtered and washed with pre-cooled n-heptane (100 mL). The obtained solid was dried at 30-40°C under reduced pressure to afford 75 g of the title compound.
Yield: 90% of theory;
Purity: 99.93%
Evample-2: Process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate:
Lorcaserin hemitartrate monohydrate salt (100 g) was suspended in ethyl acetate (200 mL) and DM water (200mL) at 20-30°C. The above suspension was cooled to 10-15°C. 40% w/w Sodium hydroxide solution (38.13 g) was slowly added for about 30 mins to the reaction mixture at 10-15°C and stirred for 30 minutes. The reaction mass temperature was raised to 20-25°C. Organic layer was separated and the aqueous layer was extracted with ethyl acetate (200 mL). Combined the organic layer and the organic layer was washed with
20% aqueous sodium chloride (400 mL). The solvent from the organic layer was evaporated under reduced pressure at below 40°C to afford oily material. The oily material is dissolved in ethyl acetate (200 mL) at 20-30°C. The reaction mass was cooled to 0-5°C. Ethyl acetate-hydrogen chloride (15% w/w, 101.21 g) was slowly added for about 30 mins to the reaction mixture at 0-5°C. n-heptane (600 mL) was slowly added for about 30 mins at 0-5°C and stirred for 3 hours at same temperature, The reaction mass was filtered and washed with pre-cooled n-heptane (100 mL). The obtained solid was dried at 30-40°C under reduced pressure to afford 76 g of the title compound. Yield: 90% of theory;
Purity: 99.95%
Claims
1. A process for the preparation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la), which comprises,
(i) providing a solution of Lorcaserin base in a solvent;
(ϋ) if water is present, removing water from the reaction mixture;
(iii) adding hydrogen chloride to the reaction mixture;
(iv) combining the reaction mixture with a suitable anti-solvent; and
(v) isolating the crystalline Lorcaserin hydrochloride hemihydrate of Formula (la).
2. The process as claimed in claim 1 , wherein solvent used in step (i) is selected from the group comprising ester, halogenated hydrocarbon, ketone, aromatic hydrocarbon or mixture thereof.
3. The process according to claim 2, wherein ester comprises from ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate, t-butyl acetate, methyl acetate; halogenated hydrocarbon comprises from dichloromethane, 1 ,2-dichloroethane, chloroform, carbon tetrachloride; ketone comprises from acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, methyl-pentane-2-one; aromatic hydrocarbon comprises from toluene, m-xylene, o-xylene, p-xylene or mixtures thereof.
4. The process as claimed in claim 1 , wherein the step-(ii) is carried out by azeotropic distillation.
5. The process as claimed in claim 1, wherein step-(iii) is carried out in presence of a solvent selected from the group comprising ester, alcohol or mixtures thereof.
6. The process as claimed in claim 5, wherein ester is selected from the group comprising ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate, t-butyl acetate, methyl acetate or mixtures thereof.
7. The process as claimed in claim 5, wherein alcohol is selected from the group comprising methanol, ethanol, ethylene glycol, 1-propanol, 2-propanol (isopiopyi alcohol), 2-methoxyethanol, 1-butanol, 2-butanol or mixtures thereof.
8. The process as claimed in claim 1, wherein anti-solvent used in step-(iv) comprises cyclohexane, pentane, hexane, toluene, cycloheptane, methyl cyclohexane, heptane or mixture thereof.
9. The process as claimed in claim I, wherein isolation of crystalline Lorcaserin hydrochloride hemihydrate of Formula (la) by conventional techniques such as filtration and dried the product.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16767827.5A EP3273967A4 (en) | 2015-03-24 | 2016-03-18 | A process for the preparation of lorcaserin hydrochloride |
| US15/741,722 US10308611B2 (en) | 2015-03-24 | 2016-03-18 | Process for the preparation of Lorcaserin hydrochloride |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1487/CHE/2015 | 2015-03-24 | ||
| IN1487CH2015 | 2015-03-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2016151451A1 true WO2016151451A1 (en) | 2016-09-29 |
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ID=56979154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2016/051535 WO2016151451A1 (en) | 2015-03-24 | 2016-03-18 | A process for the preparation of lorcaserin hydrochloride |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US10308611B2 (en) |
| EP (1) | EP3273967A4 (en) |
| WO (1) | WO2016151451A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478506A (en) * | 2016-09-30 | 2017-03-08 | 山东科兴生物制品有限公司 | The preparation method of half light green Ka Selin hydrochlorate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007120517A2 (en) * | 2006-04-03 | 2007-10-25 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates related thereto |
| WO2012030927A2 (en) * | 2010-09-01 | 2012-03-08 | Arena Pharmaceuticals, Inc. | Modified-release dosage forms of 5-ht2c agonists useful for weight management |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103601645B (en) * | 2013-11-07 | 2016-05-25 | 上海适济生物科技有限公司 | The preparation method of 1-(phenethyl amino) propane-2-alcohol compound or its salt |
-
2016
- 2016-03-18 US US15/741,722 patent/US10308611B2/en not_active Expired - Fee Related
- 2016-03-18 WO PCT/IB2016/051535 patent/WO2016151451A1/en active Application Filing
- 2016-03-18 EP EP16767827.5A patent/EP3273967A4/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007120517A2 (en) * | 2006-04-03 | 2007-10-25 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates related thereto |
| US8168782B2 (en) * | 2006-04-03 | 2012-05-01 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and intermediates related thereto |
| WO2012030927A2 (en) * | 2010-09-01 | 2012-03-08 | Arena Pharmaceuticals, Inc. | Modified-release dosage forms of 5-ht2c agonists useful for weight management |
Non-Patent Citations (1)
| Title |
|---|
| See also references of EP3273967A4 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478506A (en) * | 2016-09-30 | 2017-03-08 | 山东科兴生物制品有限公司 | The preparation method of half light green Ka Selin hydrochlorate |
| CN106478506B (en) * | 2016-09-30 | 2019-03-15 | 山东科兴生物制品有限公司 | The preparation method of half light green Ka Selin hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3273967A1 (en) | 2018-01-31 |
| US10308611B2 (en) | 2019-06-04 |
| US20180194734A1 (en) | 2018-07-12 |
| EP3273967A4 (en) | 2018-09-12 |
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