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WO2018154516A1 - Process for the preparation of pomalidomide - Google Patents

Process for the preparation of pomalidomide Download PDF

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Publication number
WO2018154516A1
WO2018154516A1 PCT/IB2018/051157 IB2018051157W WO2018154516A1 WO 2018154516 A1 WO2018154516 A1 WO 2018154516A1 IB 2018051157 W IB2018051157 W IB 2018051157W WO 2018154516 A1 WO2018154516 A1 WO 2018154516A1
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WIPO (PCT)
Prior art keywords
formula
compound
pomalidomide
preparation
dione
Prior art date
Application number
PCT/IB2018/051157
Other languages
French (fr)
Inventor
Dhiren Chandra BARMAN
Sita RAM
Mantu RAJBANGSHI
Asok Nath
Mohan Prasad
Original Assignee
Sun Pharmaceutical Industries Limited
Priority date (The priority date 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 date listed.)
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Publication of WO2018154516A1 publication Critical patent/WO2018154516A1/en

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    • 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

Definitions

  • the present invention relates to a process for the preparation of pomalidomide.
  • the present invention also provides a process for the preparation of 2-(2,6-dioxopiperidin- 3-yl)-4-nitro- lH-isoindole-l ,3(2H)-dione, a compound of Formula II and its use for the preparation of pomalidomide.
  • Pomalidomide chemically is (R5)-4-amino-2-(2,6-dioxopiperidin-3-yl)- isoindoline-l ,3-dione, represented by Formula I.
  • Pomalidomide is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
  • U.S. Patent No. 5,635,517 discloses a process for the preparation of pomalidomide by reducing 2-(2,6-dioxopiperidin-3-yl)-4-nitro-lH-isoindole-l ,3(2H)-dione of Formula II.
  • Chinese Patent No. CN103804350B describes a process for the preparation of pomalidomide by coupling 3-aminopiperidine-2,6-dione hydrochloride of Formula III with 4-nitro-lH-isoindole-l,3(2H)-dione of Formula IV in the presence of 1,1- carbonyldiimidazole and triethylamine in toluene.
  • PCT Publication No. WO2015/075694A1 describes a process for the preparation of pomalidomide by reacting 3-nitrophthalic acid of Formula B
  • the present invention relates to a process for the preparation of pomalidomide.
  • the present invention also provides a process for the preparation of 2-(2,6-dioxopiperidin- 3-yl)-4-nitro-lH-isoindole-l,3(2H)-dione, a compound of Formula II and its use for the preparation of pomalidomide.
  • the present invention provides an efficient, cost-effective and commercially viable process for the preparation of pomalidomide.
  • the present invention provides
  • a first aspect of the present invention provides a process for the preparation of 2- (2,6-dioxopiperidin-3-yl)-4-nitro-lH-isoindole-l,3(2H)-dione of Formula II,
  • a second aspect of the present invention provides a process for the preparation of pomalidomide of Formula I,
  • the compound of Formula III may be prepared by any method known in the art, for example, the method described in Bioorganic Medicinal Chemistry Letters 1999, pp. 1625-30 or by the method as disclosed herein.
  • the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 70°C to about 120°C. In an embodiment, the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 75°C to about 100°C. In another embodiment, the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 78°C to about 90°C. In another embodiment, the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 80°C to about 85 °C.
  • the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out for about one hour to about 10 hours. In an embodiment, the coupling of Formula III or its salt with the compound of Formula IV is carried out for about 2 hours to about 8 hours. In another embodiment, the coupling of Formula III or its salt with the compound of Formula IV is carried out for about 2.5 hours to about 5 hours.
  • the compound of Formula II may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, and recrystallization.
  • the compound of Formula II may be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, suck drying, air drying, or agitated thin film drying.
  • the compound of Formula II is reduced to pomalidomide of Formula I by the processes known in the art, for example, as disclosed in U.S. Patent No. 5,635,517.
  • the purification of pomalidomide of Formula I is carried out in an organic solvent.
  • the organic solvent is selected from dimethylsulf oxide, dimethylacetamide, N- methylpyrrolidone, ethyl acetate, methyl acetate, dichloromethane, ethylene chloride or a mixture thereof.
  • the purification of pomalidomide of Formula I is carried out at a temperature of about 40°C to about 70°C. In an embodiment, the purification of pomalidomide of Formula I is carried out at a temperature of about 45°C to about 65°C. In another embodiment, the purification of pomalidomide of Formula I is carried out at a temperature of about 50°C to about 60°C. In another embodiment, the purification of pomalidomide of Formula I is carried out at a temperature of about 50°C to about 55°C.
  • the purification of pomalidomide of Formula I is carried out for about 20 minutes to about 3 hours. In an embodiment, the purification of pomalidomide of Formula I is carried out for about 30 minutes to about 2 hours. In another embodiment, the purification of pomalidomide of Formula I is carried out for about 30 minutes to about one hour.
  • Step a Preparation of A ⁇ (benzyloxy carbonyl1-L-glutamine
  • a solution of sodium hydroxide (27.4 g) in water (300 mL) was added at 25°C to 30°C to a mixture of L-glutamine (100 g) and toluene (300 mL) to obtain a reaction mixture.
  • Benzyl chloroformate (50% solution in toluene; 420 g) was added to the reaction mixture slowly over a period of 60 minutes to 90 minutes while maintaining the pH to 11.0 to 12.0 with simultaneous addition of aqueous sodium hydroxide solution (120 mL; 31.5 g sodium hydroxide dissolved in 120 mL of de-ionized water).
  • Step b Preparation of benzyl (2,6-dioxopiperidin-3-yl)carbamate
  • Benzyl (2,6-dioxopiperidin-3-yl)carbamate (100 g; obtained in Step b) was added to methanol (1000 mL) and the mixture was heated at 50°C to 55°C to obtain a clear solution.
  • the solution was cooled to 25 °C to 30°C and then 10% Palladium on carbon (10 g; 50% wet) was added.
  • the solution was hydrogenated with 3.0 kg/cm 2 to 3.5 kg/cm 2 hydrogen pressure at 25 °C to 30°C for 2 hours to 3 hours.
  • the catalyst was removed by filtration. Concentrated hydrochloric acid (100 mL) was added to the filtrate and then stirred for 60 minutes to 90 minutes at 25°C to 30°C.
  • reaction mixture was concentrated at 40°C to 45 °C under reduced pressure.
  • Methanol 100 mL was added to the residue and then stirred for 60 minutes at 10°C to 15°C to obtain a slurry.
  • the slurry was filtered and the wet solid obtained was dried at 50°C under reduced pressure to obtain the title compound.
  • the slurry was slowly cooled to 25 °C to 30°C and then stirred for 30 minutes at 25°C to 30°C.
  • the slurry was filtered to obtain a wet solid.
  • the wet solid was dried at 50°C to 55°C under reduced pressure to obtain the title compound.
  • Pomalidomide (100 g; obtained in Example 3) was dissolved in dimethyl sulfoxide (DMSO) (400 mL) at 50°C to 60°C to obtain a solution.
  • DMSO dimethyl sulfoxide
  • the solution was cooled to 40°C to 45°C and then filtered followed by washing with DMSO (100 mL).
  • the combined filtrate was heated to 60°C to 65 °C and then water (500 mL) was added slowly over a period of 30 minutes to 60 minutes.
  • the slurry was stirred at 60°C to 65 °C for 60 minutes.
  • the slurry was then cooled slowly to 25°C to 30°C and then filtered to obtain a wet solid.
  • the wet solid was washed with water (2x200 mL) and then dried at 50°C to 55°C under reduced pressure to obtain pomalidomide. Yield: 98 g (98%)

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a process for the preparation of pomalidomide. The present invention also provides a process for the preparation of 2-(2,6-dioxopiperidin-3-yl)-4-nitro-1H-isoindole-1,3(2H)-dione, a compound of Formula II and its use for the preparation of pomalidomide. The pomalidomide may be made having a yield greater than 97% and the 2-(2,6-dioxopiperidin-3-yl)-4-nitro-1H-isoindole-1,3(2H)-dione (Formula II) may be made having a yield greater than 88%.

Description

PROCESS FOR THE PREPARATION OF POMALIDOMIDE
Field of the Invention
The present invention relates to a process for the preparation of pomalidomide. The present invention also provides a process for the preparation of 2-(2,6-dioxopiperidin- 3-yl)-4-nitro- lH-isoindole-l ,3(2H)-dione, a compound of Formula II and its use for the preparation of pomalidomide.
Background of the Invention
Pomalidomide, chemically is (R5)-4-amino-2-(2,6-dioxopiperidin-3-yl)- isoindoline-l ,3-dione, represented by Formula I.
Figure imgf000002_0001
Formula I
Pomalidomide is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
U.S. Patent No. 5,635,517 discloses a process for the preparation of pomalidomide by reducing 2-(2,6-dioxopiperidin-3-yl)-4-nitro-lH-isoindole-l ,3(2H)-dione of Formula II.
Figure imgf000002_0002
Formula II U.S. Patent No. '517 further describes the preparation of 2-(2,6-dioxopiperidin-3- yl)-4-nitro-lH-isoindole-l,3(2H)-dione of Formula II by coupling hydrochloride salt of 3- aminopiperidine-2,6-dione of Formula III
Figure imgf000003_0001
Formula III
with 4-nitro-lH-isoindole-l,3(2H)-dione of Formula IV
Figure imgf000003_0002
Formula IV
in the presence of sodium acetate and glacial acetic acid.
Chinese Patent No. CN103804350B describes a process for the preparation of pomalidomide by coupling 3-aminopiperidine-2,6-dione hydrochloride of Formula III with 4-nitro-lH-isoindole-l,3(2H)-dione of Formula IV in the presence of 1,1- carbonyldiimidazole and triethylamine in toluene.
U.S. Patent No. 7,994,327 describes a process for the preparation of pomalidomide by reacting 3-aminophthalic acid hydrochloride of Formula A
Figure imgf000003_0003
Formula A
with 3-aminopiperidine-2,6-dione hydrochloride of Formula III in the presence of triethylamine and acetonitrile.
PCT Publication No. WO2015/075694A1 describes a process for the preparation of pomalidomide by reacting 3-nitrophthalic acid of Formula B
Figure imgf000004_0001
Formula B
with 3-aminopiperidine-2,6-dione hydrochloride of Formula III in the presence of 1,1- carbonyldiimidazole and acetonitrile.
There is a need in the art to develop an improved process for the preparation of pomalidomide.
Summary of the Invention
The present invention relates to a process for the preparation of pomalidomide. The present invention also provides a process for the preparation of 2-(2,6-dioxopiperidin- 3-yl)-4-nitro-lH-isoindole-l,3(2H)-dione, a compound of Formula II and its use for the preparation of pomalidomide.
The present invention provides an efficient, cost-effective and commercially viable process for the preparation of pomalidomide. The present invention provides
pomalidomide having yield more that 97% and 2-(2,6-dioxopiperidin-3-yl)-4-nitro-lH- isoindole-l,3(2H)-dione, a compound of Formula II having yield more than 88%.
Detailed Description of the Invention
The term "about," as used herein, refers to any value which lies within the range defined by a number up to ±10% of the value.
A first aspect of the present invention provides a process for the preparation of 2- (2,6-dioxopiperidin-3-yl)-4-nitro-lH-isoindole-l,3(2H)-dione of Formula II,
Figure imgf000004_0002
Formula II
comprising coupling a compound of Formula III or its salt
Figure imgf000005_0001
Formula III
with a compound of Formula IV
Figure imgf000005_0002
Formula IV
in the presence of 1,1-carbonyldiimidazole and acetonitrile.
A second aspect of the present invention provides a process for the preparation of pomalidomide of Formula I,
Figure imgf000005_0003
Formula I
comprising
a) coupling a compound of Formula III or its salt
Figure imgf000005_0004
Formula III
with a compound of Formula IV
Figure imgf000006_0001
Formula IV
in the presence of 1,1-carbonyldiimidazole and acetonitrile to obtain a compound of Formula II; and
Figure imgf000006_0002
Formula II
b) reducing the compound of Formula II to obtain pomalidomide of Formula I.
The compound of Formula III may be prepared by any method known in the art, for example, the method described in Bioorganic Medicinal Chemistry Letters 1999, pp. 1625-30 or by the method as disclosed herein.
The coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 70°C to about 120°C. In an embodiment, the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 75°C to about 100°C. In another embodiment, the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 78°C to about 90°C. In another embodiment, the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of about 80°C to about 85 °C.
The coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out for about one hour to about 10 hours. In an embodiment, the coupling of Formula III or its salt with the compound of Formula IV is carried out for about 2 hours to about 8 hours. In another embodiment, the coupling of Formula III or its salt with the compound of Formula IV is carried out for about 2.5 hours to about 5 hours. The compound of Formula II may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, and recrystallization. The compound of Formula II may be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, suck drying, air drying, or agitated thin film drying.
The compound of Formula II is reduced to pomalidomide of Formula I by the processes known in the art, for example, as disclosed in U.S. Patent No. 5,635,517.
The purification of pomalidomide of Formula I is carried out in an organic solvent. The organic solvent is selected from dimethylsulf oxide, dimethylacetamide, N- methylpyrrolidone, ethyl acetate, methyl acetate, dichloromethane, ethylene chloride or a mixture thereof.
The purification of pomalidomide of Formula I is carried out at a temperature of about 40°C to about 70°C. In an embodiment, the purification of pomalidomide of Formula I is carried out at a temperature of about 45°C to about 65°C. In another embodiment, the purification of pomalidomide of Formula I is carried out at a temperature of about 50°C to about 60°C. In another embodiment, the purification of pomalidomide of Formula I is carried out at a temperature of about 50°C to about 55°C.
The purification of pomalidomide of Formula I is carried out for about 20 minutes to about 3 hours. In an embodiment, the purification of pomalidomide of Formula I is carried out for about 30 minutes to about 2 hours. In another embodiment, the purification of pomalidomide of Formula I is carried out for about 30 minutes to about one hour.
While the present invention has been described in terms of its specific aspects and embodiments, certain modifications and equivalents will be apparent to those skilled in the art, and are intended to be included within the scope of the present invention.
The following examples are for illustrative purposes only and should not be construed as limiting the scope of the invention in any way.
EXAMPLES
Example 1 : Preparation of 3-aminopiperidine-2,6-dione hydrochloride (Hydrochloride salt of Formula III)
Step a: Preparation of A^ (benzyloxy carbonyl1-L-glutamine A solution of sodium hydroxide (27.4 g) in water (300 mL) was added at 25°C to 30°C to a mixture of L-glutamine (100 g) and toluene (300 mL) to obtain a reaction mixture. Benzyl chloroformate (50% solution in toluene; 420 g) was added to the reaction mixture slowly over a period of 60 minutes to 90 minutes while maintaining the pH to 11.0 to 12.0 with simultaneous addition of aqueous sodium hydroxide solution (120 mL; 31.5 g sodium hydroxide dissolved in 120 mL of de-ionized water). Water was added to the reaction mixture and the layers were separated. The aqueous layer was washed with toluene (300 mL). The pH of the aqueous layer was adjusted to 1.0 to 1.5 with dilute hydrochloric acid (100 mL) to obtain a slurry. The slurry was cooled to 0°C to 5°C and then stirred for one hour. The product so obtained was filtered, washed with water (2x200 mL) to obtain a wet solid. The wet solid was dried in an air oven at 50°C to 55°C to obtain the title compound.
Yield: 170 g (88.5%)
Step b: Preparation of benzyl (2,6-dioxopiperidin-3-yl)carbamate
1,1-Carbonyldiimidazole (81 g) was added to a slurry of N2-
[(benzyloxy)carbonyl]-L-glutamine (100 g; obtained in Step a) in ethyl acetate (1000 mL) and then heated at 76°C to 80°C for 2 hours to 3 hours. The reaction mixture was concentrated at 50°C to 55 °C under reduced pressure to obtain a residue. Water (800 mL) was added to the residue at 25°C to 30°C to obtain a slurry. The slurry was stirred at 10°C to 15°C for one hour and then filtered and dried at 50°C to 55°C to obtain the title compound.
Yield: 75 g (80%)
Step c: Preparation of 3-aminopiperidine-2,6-dione hydrochloride
Benzyl (2,6-dioxopiperidin-3-yl)carbamate (100 g; obtained in Step b) was added to methanol (1000 mL) and the mixture was heated at 50°C to 55°C to obtain a clear solution. The solution was cooled to 25 °C to 30°C and then 10% Palladium on carbon (10 g; 50% wet) was added. The solution was hydrogenated with 3.0 kg/cm2 to 3.5 kg/cm2 hydrogen pressure at 25 °C to 30°C for 2 hours to 3 hours. The catalyst was removed by filtration. Concentrated hydrochloric acid (100 mL) was added to the filtrate and then stirred for 60 minutes to 90 minutes at 25°C to 30°C. The reaction mixture was concentrated at 40°C to 45 °C under reduced pressure. Methanol (100 mL) was added to the residue and then stirred for 60 minutes at 10°C to 15°C to obtain a slurry. The slurry was filtered and the wet solid obtained was dried at 50°C under reduced pressure to obtain the title compound.
Yield: 56 g (90%)
Example 2: Preparation of 2-(2,6-dioxopiperidin-3-yl')-4-nitro-lH-isoindole-l,3(2H)-dione (Formula II)
4-Nitro-lH-isoindole-l, 3(2H)-dione (117.3 g; Formula IV) followed by 1,1- carbonyldiimidazole (138.1 g) were added to a slurry of 3-aminopiperidine-2,6-dione hydrochloride (100 g, Formula III; obtained in Example 1) in acetonitrile (800 mL) to obtain a reaction mixture. The reaction mixture was heated to reflux at 80°C to 82°C and then stirred for 2 hours. 1,1-Carbonyldiimidazole (19.8 g) was further added to the reaction mixture twice over an interval of one hour. The reaction mixture was cooled to 25 °C to 30°C and then stirred for 30 minutes. The product obtained was filtered and the wet solid obtained was dried at 50°C to 55°C under reduced pressure to obtain the title compound.
Yield: 162 g (88%)
Example 3: Preparation of pomalidomide (Formula I)
10% Palladium on carbon (50% wet; 5 g) was added to a solution of 2-(2,6- dioxopiperidin-3-yl)-4-nitro-lH-isoindole-l,3(2H)-dione (100 g; Formula II; obtained in Example 2) in N, N-dimethylformamide (1000 mL). The solution was hydrogenated with 3.0 kg/cm2 to 3.5 kg/cm2 hydrogen pressure for 2 hours to 3 hours at 25°C to 30°C. The catalyst was removed by filtration and the filtrate was treated with activated carbon. The filtrate was heated to 50°C to 55°C and then water was added slowly at 50°C to 55°C to obtain a slurry. The slurry was slowly cooled to 25 °C to 30°C and then stirred for 30 minutes at 25°C to 30°C. The slurry was filtered to obtain a wet solid. The wet solid was dried at 50°C to 55°C under reduced pressure to obtain the title compound.
Yield: 85 g (94%)
Example 4: Purification of pomalidomide (Formula I)
Pomalidomide (100 g; obtained in Example 3) was dissolved in dimethyl sulfoxide (DMSO) (400 mL) at 50°C to 60°C to obtain a solution. The solution was cooled to 40°C to 45°C and then filtered followed by washing with DMSO (100 mL). The combined filtrate was heated to 60°C to 65 °C and then water (500 mL) was added slowly over a period of 30 minutes to 60 minutes. The slurry was stirred at 60°C to 65 °C for 60 minutes. The slurry was then cooled slowly to 25°C to 30°C and then filtered to obtain a wet solid. The wet solid was washed with water (2x200 mL) and then dried at 50°C to 55°C under reduced pressure to obtain pomalidomide. Yield: 98 g (98%)

Claims

Claims
A process for the preparation of 2-(2,6-dioxopiperidin-3-yl)-4-nitro-lH-isoindole l,3(2H)-dione of Formula II,
Figure imgf000011_0001
Formula II
comprising coupling a com ound of Formula III or its salt
Figure imgf000011_0002
Formula III
with a compound of Formula IV
Figure imgf000011_0003
Formula IV
in the presence of 1,1-carbonyldiimidazole and acetonitrile.
A process for the preparation of pomalidomide of Formula I,
Figure imgf000011_0004
Formula I
comprising a) coupling a compound of Formula III or its salt
Figure imgf000012_0001
Formula III
with a compound of Formula IV
Figure imgf000012_0002
Formula IV
in the presence of 1,1-carbonyldiimidazole and acetonitrile to obtain a compound of Formula II; and
Figure imgf000012_0003
Formula II
b) reducing the compound of Formula II to obtain pomalidomide of Formula I.
3. The process according to claim 1, wherein the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of 70°C to 120°C.
4. The process according to claim 2, wherein the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out at a temperature of 70°C to 120°C. The process according to claim 1, wherein the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out for one hour to 10 hours.
The process according to claim 2, wherein the coupling of the compound of Formula III or its salt with the compound of Formula IV is carried out for one hour to 10 hours.
PCT/IB2018/051157 2017-02-23 2018-02-23 Process for the preparation of pomalidomide WO2018154516A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111675648A (en) * 2020-06-29 2020-09-18 济南久隆医药科技有限公司 Synthetic method of pomalidomide intermediate

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US5635517A (en) * 1996-07-24 1997-06-03 Celgene Corporation Method of reducing TNFα levels with amino substituted 2-(2,6-dioxopiperidin-3-yl)-1-oxo-and 1,3-dioxoisoindolines
US20070004920A1 (en) * 2005-06-30 2007-01-04 Celgene Corporation An Orgnization Of The State New Jersey Processes for the preparation of 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione compounds
WO2013126326A1 (en) * 2012-02-21 2013-08-29 Celgene Corporation Solid forms of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione, compositions and methods of use thereof
US20160362391A1 (en) * 2013-11-25 2016-12-15 Mylan Laboratories Ltd. Improved Process for the Preparation of Pomalidomide and its Purification

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5635517A (en) * 1996-07-24 1997-06-03 Celgene Corporation Method of reducing TNFα levels with amino substituted 2-(2,6-dioxopiperidin-3-yl)-1-oxo-and 1,3-dioxoisoindolines
US5635517B1 (en) * 1996-07-24 1999-06-29 Celgene Corp Method of reducing TNFalpha levels with amino substituted 2-(2,6-dioxopiperidin-3-YL)-1-oxo-and 1,3-dioxoisoindolines
US20070004920A1 (en) * 2005-06-30 2007-01-04 Celgene Corporation An Orgnization Of The State New Jersey Processes for the preparation of 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione compounds
WO2013126326A1 (en) * 2012-02-21 2013-08-29 Celgene Corporation Solid forms of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione, compositions and methods of use thereof
US20160362391A1 (en) * 2013-11-25 2016-12-15 Mylan Laboratories Ltd. Improved Process for the Preparation of Pomalidomide and its Purification

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111675648A (en) * 2020-06-29 2020-09-18 济南久隆医药科技有限公司 Synthetic method of pomalidomide intermediate
CN111675648B (en) * 2020-06-29 2023-04-14 济南久隆医药科技有限公司 Synthetic method of pomalidomide intermediate

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