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WO2022195500A1 - Procédé de préparation d'un intermédiaire de tosylate de lumatépérone - Google Patents

Procédé de préparation d'un intermédiaire de tosylate de lumatépérone Download PDF

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Publication number
WO2022195500A1
WO2022195500A1 PCT/IB2022/052370 IB2022052370W WO2022195500A1 WO 2022195500 A1 WO2022195500 A1 WO 2022195500A1 IB 2022052370 W IB2022052370 W IB 2022052370W WO 2022195500 A1 WO2022195500 A1 WO 2022195500A1
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Prior art keywords
tosylate intermediate
lumateperone tosylate
pyrido
benzyl
carboxylate
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Inventor
Savankumar Dahyabhai PATEL
Anandkumar Balchand JAIN
Jignasu Thakorbhai DESAI
Rajeev Ramchandra DUBEY
Ajit Kumar CHOUBEY
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Ami Organics Ltd
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Ami Organics Ltd
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Publication of WO2022195500A1 publication Critical patent/WO2022195500A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/16—Peri-condensed systems

Definitions

  • the present disclosure relates to a process for the preparation of lumateperone tosylate intermediate.
  • Benzyl,3-methyl-2-oxo-2,3,9,10-tetrahydro-lH-pyrido[3',4’:4,5]pyrrolo[l,2,3-de] quinoxaline-8(7H) carboxylate represented as Formula (I) is the key raw material for the preparation of lumateperone tosylate drug which is used for the treatment of schizophrenia.
  • the conventional route for preparing lumateperone tosylate intermediate includes the use of high-cost reagents such as tris(dibenzylideneacetone)dipalladium (Pd (dba) ) as a metal catalyst and Xantphos that produces hazardous waste, Hence, such conventional processes are not economic and not environment friendly.
  • An object of the present disclosure is to provide a process for the preparation of benzyl, 3- methyl-2-oxo-2,3,9,10-tetrahydro-lH-pyrido[3',4':4,5]pyrrolo[l,2,3-de] quinoxaline-8(7H) carboxylate (I) (lumateperone tosylate intermediate).
  • Another object of the present disclosure is to provide a process for the preparation of benzyl,3-methyl-2-oxo-2,3,9,10-tetrahydro-lH-pyrido[3',4':4,5]pyrrolo[l,2,3-de] quinoxaline-8(7H) carboxylate (I) with a comparatively high yield and high purity.
  • Still another object of the present disclosure is to provide a simple, economical and eco- friendly process for preparation of benzyl 3-methyl-2-oxo-2,3,9,10-tetrahydro-lH- pyrido[3',4':4,5]pyrrolo[l,2,3-de]quinoxaline-8(7H) carboxylate.
  • the present disclosure relates to a process for the preparation of lumateperone tosylate intermediate.
  • the process comprises mixing benzyl 6-bromo-5-(2-(methylamino)-2- oxoethyl)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b] indole-2-carboxylate with predetermined amounts of a base, a metal halide, and a catalyst in a predetermined amount of a fluid medium under stirring to obtain a reaction mixture.
  • the mixture is heated to a first predetermined temperature for a first predetermined time period to obtain a product mixture comprising a crude benzyl,3-methyl-2-oxo-2,3,9,10-tetrahydro- lHpyrido[3',4':4,5]pyrrolo[l,2,3-de]quinoxaline-8(7H) carboxylate (lumateperone tosylate intermediate).
  • the crude lumateperone tosylate intermediate is isolated and purified to obtain a pure lumateperone tosylate intermediate.
  • the present disclosure relates to a process for the preparation of lumateperone tosylate intermediate.
  • Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
  • Benzyl,3-methyl-2-oxo-2,3,9,10-tetrahydro-lH-pyrido[3',4':4,5]pyrrolo[l,2,3-de] quinoxaline-8(7H) carboxylate represented as Formula (I) is used as an intermediate in the preparation of lumateperone tosylate drug which is used for the treatment of schizophrenia.
  • the conventional route for preparing lumateperone tosylate intermediate includes the use of high-cost reagents such as tris(dibenzylideneacetone)dipalladium (Pd (dba) ) as a metal catalyst and Xantphos that produces hazardous waste, Hence, such conventional processes are not economic and not environment friendly.
  • the present disclosure provides a process for the preparation of lumateperone tosylate intermediate.
  • the present disclosure relates to a process for the preparation of benzyl, 3- methyl-2-oxo-2,3,9,10-tetrahydro-lH-pyrido[3’,4’:4,5]pyrrolo[l,2,3-de]quinoxaline-
  • the process for the preparation of lumateperone tosylate intermediate comprises the following steps: i. mixing benzyl 6-bromo-5-(2-(methylamino)-2-oxoethyl)-l,3,4,5-tetrahydro-2H- pyrido[4,3-b]indole-2-carboxylate with predetermined amounts of a base, a metal halide, and a catalyst in a predetermined amount of a fluid medium under stirring to obtain a reaction mixture; ii.
  • reaction mixture heating the reaction mixture to a first predetermined temperature for a first predetermined time period to obtain a product mixture comprising a crude benzyl 3- methyl-2-oxo-2,3,9,10-tetrahydro-lH pyrido[3’,4’:4,5]pyrrolo [1,2,3-de] quinoxaline- 8(7H)-carboxylate (crude lumateperone tosylate intermediate); and iii. isolating and purifying the crude lumateperone tosylate intermediate to obtain a pure lumateperone tosylate intermediate.
  • benzyl 6-bromo-5-(2-(methylamino)-2-oxoethyl)-l, 3, 4, 5-tetrahydro-2H- pyrido [4, 3-b] indole-2-carboxylate is mixed with predetermined amounts of a base, a metal halide, and a catalyst in a predetermined amount of a fluid medium under stirring to obtain a reaction mixture.
  • the base is selected from the group consisting of potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide.
  • the base is potassium carbonate.
  • a molar ratio of benzyl 6-bromo-5-(2- (methylamino)-2-oxoethyl)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate to the base is in the range of 1:2 to 1:3.
  • the molar ratio of benzyl 6- bromo-5-(2-(methylamino)-2-oxoethyl)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2- carboxylate to the base is 1:2.3.
  • the metal halide is selected from the group consisting of copper iodide, copper bromide (CuBr), copper chloride (CuCl), copper acetate (Cu(OAc) 2 ), copper sulphate (CuSCb) and copper oxide (CuO).
  • the metal halide is copper iodide.
  • a molar ratio of benzyl 6-bromo-5-(2- (methyIamino)-2-oxoethyI)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indoIe-2-carboxyIate to the metal halide is in the range of 1:0.1 to 1:0.3.
  • the molar ratio of benzyl 6-bromo-5-(2-(methyIamino)-2-oxoethyI)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indoIe- 2-carboxylate to the metal halide is 1:0.24.
  • the catalyst is selected from the group consisting of N,N’-dimethyIethyIenediamine (DMEDA), l,8-DiazabicycIo(5.4.0)undec-7-ene (DBU), l,5-DiazabicycIo(4.3.0)non-5-ene (DBN), I,4-diazabicycIo[2.2.2]octane (DABCO), imidazolium carbene, 4- (dimethylamino)pyridine, TMEDA 1,2-diamine and 1,2-aminoaIcohoI.
  • the catalyst is N,N’-dimethyIethyIenediamine (DMEDA).
  • the catalyst is l,8-DiazabicycIo(5.4. 0)undec-7-ene (DBU).
  • a molar ratio of benzyl 6-bromo-5-(2- (methyIamino)-2-oxoethyI)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indoIe-2-carboxyIate to the catalyst is in the range of 1:0.5 to 1:1.5.
  • the molar ratio of benzyl 6-bromo-5-(2-(methyIamino)-2-oxoethyI)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indoIe- 2-carboxylate to DMEDA is 1:0.73.
  • the molar ratio of benzyl 6-bromo-5-(2-(methyIamino)-2-oxoethyI)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indoIe- 2-carboxylate to DBU is 1:0.9.
  • the molar ratio of benzyl 6-bromo-5-(2-(methyIamino)-2-oxoethyI)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indoIe- 2-carboxylate to DMDEA is 1:1.14.
  • the fluid medium is selected from the group consisting of dimethyl sulfoxide (DMSO), dimethyl form amide (DMF) and toluene.
  • DMSO dimethyl sulfoxide
  • DMF dimethyl form amide
  • toluene toluene.
  • the amount of fluid medium is in the range of 1 litre to 5 litres per mole of benzyl 6-bromo- 5-(2-(methylamino)-2-oxoethyl)-l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate.
  • the amount of fluid medium is 2.3 litres per mole of benzyl 6-bromo-5-(2-(methylamino)-2-oxoethyl)-l,3,4,5-tetrahydro-2H- pyrido[4,3-b]indole-2-carboxylate.
  • reaction mixture is heated to a first predetermined temperature for a first predetermined time period to obtain a product mixture comprising a crude benzyI-3-methyI- 2-oxo-2,3,9,10-tetrahydro-lH pyrido[3',4':4,5]pyrroIo [1,2,3-de] quinoxaIine-8(7H)- carboxylate (crude lumateperone tosylate intermediate).
  • the first predetermined temperature is in the range of 80 °C to 120 °C. In an exemplary embodiment, the first predetermined temperature is 85 °C. In another exemplary embodiment, the first predetermined temperature is 120 °C.
  • the first predetermined time period is in the range of 10 hours to 25 hours. In an exemplary embodiment, the first predetermined time period is 16 hours. In another exemplary embodiment, the first predetermined time period is 12 hours. In yet another exemplary embodiment, the first predetermined time period is 24 hours.
  • the crude lumateperone tosylate intermediate is isolated and purified to obtain a pure lumateperone tosylate intermediate.
  • the step of isolation of crude lumateperone tosylate intermediate comprises the following sub-steps:
  • the so obtained lumateperone tosylate intermediate is subjected to further purification step when toluene is used as a fluid medium.
  • the purification of the so obtained lumateperone tosylate intermediate is not required when DMSO/DMF is used as a fluid medium.
  • the further purification step when toluene is used as the fluid medium comprises the following sub-steps: a. dissolving the washed wet cake obtained in the isolation sub-step (ii) in water to obtain a slurry; b. heating the slurry to a fourth predetermined temperature for a second predetermined time period to obtain a heated slurry; c. cooling the heated slurry to a fifth predetermined temperature followed by filtration to obtain a residue mass and a filtrate; and d. drying the residue mass at the third predetermined temperature to obtain a pure lumateperone tosylate intermediate having a moisture content in the range of 0.1 % to 1 %.
  • the second predetermined temperature is in the range of 15 °C to 80 °C. In an exemplary embodiment, the second predetermined temperature is 25 °C. In another exemplary embodiment, the second predetermined temperature is 70 °C.
  • the fluid medium is selected from the group consisting of toluene, DMSO, DMF.
  • the fluid medium is toluene.
  • the fluid medium is DMSO.
  • the fluid medium is DMF.
  • the third predetermined temperature is in the range of 50 °C to 70 °C. In an exemplary embodiment, the third predetermined temperature is 60 °C.
  • the fourth predetermined temperature is in the range of 70 °C to 90 °C. In an exemplary embodiment, the fourth predetermined temperature is 80 °C.
  • the second predetermined time period is in the range of 0.5 hour to 1.5 hours. In an exemplary embodiment, the second predetermined time period is 1 hour.
  • the fifth predetermined temperature is in the range of 50 °C to 70 °C. In an exemplary embodiment, the fifth predetermined temperature is 60 °C.
  • the moisture content of the so obtained pure lumateperone tosylate intermediate is in the range of 0.1 % to 1%.
  • the lumateperone tosylate intermediate having less moisture content results in the desired quality product in next stage by using the reduction stage.
  • the process of the present disclosure provides lumateperone tosylate intermediate with a yield in the range of 45 % to 60 % and a purity in the range of 93 % to 98 %.
  • water is added to the filtrate obtained in sub-step (v) in a drop wise manner to obtain a precipitate of lumateperone tosylate intermediate.
  • the so obtained precipitated lumateperone tosylate intermediate is filtered to obtain a third wet cake.
  • the second wet cake and third wet cake so obtained are mixed together and dried at 60°C till the moisture content is 0.1 % to 1 % to obtain the pure lumateperone tosylate intermediate.
  • the present disclosure provides an alternative process for the preparation of lumateperone tosylate intermediate by using non-toxic and cheap reagents.
  • the process of the present disclosure is cost efficient, economic and environmental friendly.
  • Example 1 Preparation of lumateperone tosylate intermediate by using N.N’- dimethylethylenediamine (DMEDA) as a catalyst and DMSO as a fluid medium
  • DMEDA N.N’- dimethylethylenediamine
  • the resultant mixture was heated by slowly raising the temperature to 80 °C and further maintained at 120°C for 16 hours to obtain a product mixture comprising a crude lumateperone tosylate intermediate.
  • the reaction was monitored by checking the thin layer chromatography (TLC) of the product mixture against the starting material.
  • the so obtained product mixture was cooled to 65 °C to obtain a cooled mass.
  • the cooled mass was filtered to obtain a wet cake followed by washing with 100 ml DMSO to obtain a washed wet cake and a filtrate.
  • 1500 ml of water was added to the so obtained filtrate in a dropwise manner to obtain a precipitate of lumateperone tosylate intermediate.
  • the so obtained precipitated lumateperone tosylate intermediate was filtered to obtain a residue mass.
  • the wet cake and the residue mass were mixed together and dried at 60°C till the moisture content was 1 % to obtain the pure lumateperone tosylate intermediate.
  • the yield of pure lumateperone tosylate intermediate was 42 g (51.05 %) and the purity was
  • Example 2 Preparation of lumateperone tosylate intermediate by using 1,8- Diazabicvclo(5.9.0)undec-7-ene (DBU)as a catalyst and DMSO as a fluid medium
  • DBU 1,8- Diazabicvclo(5.9.0)undec-7-ene
  • the so obtained product mixture was cooled to 65°C to obtain a cooled mass.
  • the cooled mass was filtered to obtain a wet cake followed by washing with 100 ml DMSO to obtain a washed wet cake and a filtrate.
  • 1500 ml of water was added to the so obtained filtrate in a dropwise manner to obtain a precipitate of lumateperone tosylate intermediate.
  • the so obtained precipitated lumateperone tosylate intermediate was filtered to obtain a residue mass.
  • the wet cake and the residue mass were mixed together and dried at 60°C till the moisture content was 1 % to obtain the pure lumateperone tosylate intermediate.
  • the yield of pure lumateperone tosylate intermediate was 47.5 g (57.74 %) and the purity was 97.93 %.
  • Example 3 Preparation of lumateperone tosylate intermediate by using N.N’- dimethylethylenediamine (DMEDA)as a catalyst and DMF as a fluid medium
  • the resultant mixture was heated by slowly raising the temperature to 85 °C and further maintained at 120 °C for 24 hours to obtain a product mixture comprising a crude lumateperone tosylate intermediate.
  • the reaction was monitored by checking the thin layer chromatography (TLC) of the product mi ture against the starting material.
  • the so obtained product mixture was cooled to 65°C to obtain a cooled mass.
  • the cooled mass was filtered to obtain a wet cake followed by washing with 100 ml DMF to obtain a washed wet cake and a filtrate.
  • 1500 ml of water was added to the so obtained filtrate in a dropwise manner to obtain a precipitate of lumateperone tosylate intermediate.
  • the so obtained precipitated lumateperone tosylate intermediate was filtered to obtain a residue mass.
  • the wet cake and the residue mass were mixed together and dried at 60°C till the moisture content was 1 % to obtain the pure lumateperone tosylate intermediate.
  • the yield of pure lumateperone tosylate intermediate was 38 g (46.19 %) and the purity was 93.5 %.
  • Example 4 Preparation of lumateperone tosylate intermediate by using Diazabicvclol5.4.01undec-7-ene (DBU ) as a catalyst and DMF as a fluid medium
  • the resultant mixture was heated by slowly raising the temperature to 85 °C and further maintained at 120 °C for 24 hours to obtain a product mixture comprising a crude lumateperone tosylate intermediate.
  • the reaction was monitored by checking the thin layer chromatography (TLC) of the product mixture against the starting material.
  • the so obtained product mixture was cooled to 65°C to obtain a cooled mass.
  • the cooled mass was filtered to obtain a wet cake followed by washing with 100 ml DMF to obtain a washed wet cake and a filtrate.
  • 1500 ml of water was added to the so obtained filtrate in a dropwise manner to obtain a precipitate of lumateperone tosylate intermediate.
  • the so obtained precipitated lumateperone tosylate intermediate was filtered to obtain a residue mass.
  • the wet cake and the residue mass were mixed together and dried at 60°C till the moisture content was 1 % to obtain the pure lumateperone tosylate intermediate.
  • the yield of pure lumateperone tosylate intermediate was 41 g (49.84 %) and the purity was 94.2 %.
  • Example 5 Preparation of lumateperone tosylate intermediate by using N.N’- dimethylethylenediamine (DM EDA ) as a catalyst and toluene as a fluid medium
  • the resultant mixture was heated by slowly raising the temperature to 110 °C and further maintained at 110 °C for 20 hours to obtain a product mixture comprising a crude benzyl 3-methyl-2-oxo-2, 3, 9, 10-tetrahydro- lH-pyrido[3',4':4,5] pyrrolo [l,2,3-de]quinoxaline-8(7H)-carboxylate (I) (crude lumateperone tosylate intermediate).
  • TLC thin layer chromatography
  • the so obtained product mixture was cooled to 25 °C to obtain a cooled mass.
  • the cooled mass was filtered to obtain a wet cake followed by washing with 155 ml toluene to obtain a washed wet cake and a filtrate.
  • the so obtained washed wet cake was dissolved in 1000 ml water to obtain a slurry.
  • the slurry was heated to 80 °C and the temperature was maintained at 80 °C for 1 hour to obtain a heated slurry.
  • the heated slurry was cooled to 60 °C followed by hot filtration to obtain a residue mass and a filtrate.
  • the residue mass was further washed with 250 ml of hot water followed by drying at 60 °C till the moisture content of the residue mass was 1 % to obtain the pure lumateperone tosylate intermediate.
  • the yield of pure lumateperone tosylate intermediate was 60 g (47.05 %) and the purity was 94.6 %.
  • Example 6 Preparation of lumateperone tosylate intermediate by using DiazabicycloI5.4.01undec-7-ene (DBU) as a catalyst and toluene as a fluid medium
  • DBU DiazabicycloI5.4.01undec-7-ene
  • toluene a fluid medium
  • DBU DiazabicycloI5.4.01undec-7-ene
  • a reactor 450 ml of toluene, 100 g of benzyl 6-bromo-5-(2-(methylamino)-2-oxoethyl)- l,3,4,5-tetrahydro-2H-pyrido[4,3-b]indoIe-2-carboxyIate, 71 g of potassium carbonate, 10.5 g of copper iodide, 30 g of l,8-Diazabicyclo(5.4.
  • DBU DiazabicycloI5.4.01undec-7-ene
  • the so obtained product mixture was cooled to 25°C to obtain a cooled mass.
  • the cooled mass was filtered to obtain a wet cake followed by washing with 155 ml toluene to obtain a washed wet cake and a filtrate.
  • the so obtained washed wet cake was dissolved in 1000 ml water to obtain a slurry.
  • the slurry was heated to 80°C and the temperature was maintained at 80°C for 1 hour to obtain a heated slurry.
  • the heated slurry was cooled to 60°C followed by hot filtration to obtain a residue mass and a filtrate.
  • the residue mass was further washed with 200 ml of hot water followed by drying at 60°C till the moisture content of the residue mass was 1 % to obtain the pure lumateperone tosylate intermediate.
  • the yield of pure lumateperone tosylate intermediate was 40 g (48.62 %) and the purity was 94.9 %.
  • the objective of the present disclosure i.e. to provide a simple, economical and eco-friendly process that requires minimum time period for the preparation of lumateperone tosylate intermediate with a comparatively high yield and high purity was achieved.
  • the reason for achieving high yield and high purity of the product (lumateperone tosylate intermediate) in comparatively less time period was that the reaction was carried out in nitrogen atmosphere by using the appropriate fluid medium (DMSO/DMF) and the catalyst (DMEDA/DBU).
  • the present disclosure described hereinabove has several technical advantages including, but not limited to, the realization of a process for preparing lumateperone tosylate intermediate that: provides a comparatively high purity and high yield of the product (lumateperone tosylate intermediate); employs inexpensive reagents and is industrially feasible; and is simple and environment friendly.

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Abstract

La présente invention concerne un procédé de préparation d'un intermédiaire de tosylate de lumatépérone. Le procédé comprend la conversion de 6-bromo-5-(2- (méthylamino)-2-oxoéthyl)-1,3,4,5-tétrahydro-2H-pyrido[4,3-b]indole-2-carboxylate en un intermédiaire de tosylate de lumatépérone avec un rendement comparativement élevé et une pureté élevée. Le procédé de la présente invention est simple, utilise des réactifs peu coûteux et est respectueux de l'environnement.
PCT/IB2022/052370 2021-03-16 2022-03-16 Procédé de préparation d'un intermédiaire de tosylate de lumatépérone Ceased WO2022195500A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118566395A (zh) * 2024-08-02 2024-08-30 则正(济南)生物科技有限公司 测定甲苯磺酸卢美哌隆口崩片中杂质含量的方法、应用和系统
WO2025149870A1 (fr) * 2024-01-12 2025-07-17 Ami Organics Ltd. Sels intermédiaires de lumatépérone, leurs procédés de préparation et intermédiaire de lutépérone obtenus à partir de ceux-ci

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018031535A1 (fr) * 2016-08-09 2018-02-15 Assia Chemical Industries Ltd. Formes à l'état solide de sel de ditosylate lumateperone
WO2018189646A1 (fr) * 2017-04-10 2018-10-18 Dr. Reddy's Laboratories Limited Forme amorphe et dispersions solides de p-tosylate de lumateperone
WO2020112941A2 (fr) * 2018-11-27 2020-06-04 Teva Czech Industries S.R.O Formes à l'état solide de sels de lumatépérone et procédés de préparation de lumatépérone et de ses sels

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018031535A1 (fr) * 2016-08-09 2018-02-15 Assia Chemical Industries Ltd. Formes à l'état solide de sel de ditosylate lumateperone
WO2018189646A1 (fr) * 2017-04-10 2018-10-18 Dr. Reddy's Laboratories Limited Forme amorphe et dispersions solides de p-tosylate de lumateperone
WO2020112941A2 (fr) * 2018-11-27 2020-06-04 Teva Czech Industries S.R.O Formes à l'état solide de sels de lumatépérone et procédés de préparation de lumatépérone et de ses sels

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025149870A1 (fr) * 2024-01-12 2025-07-17 Ami Organics Ltd. Sels intermédiaires de lumatépérone, leurs procédés de préparation et intermédiaire de lutépérone obtenus à partir de ceux-ci
CN118566395A (zh) * 2024-08-02 2024-08-30 则正(济南)生物科技有限公司 测定甲苯磺酸卢美哌隆口崩片中杂质含量的方法、应用和系统

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