EP3759081A1 - Verbessertes verfahren zur herstellung von propiomazinmaleat - Google Patents

Verbessertes verfahren zur herstellung von propiomazinmaleat

Info

Publication number
EP3759081A1
EP3759081A1 EP19760246.9A EP19760246A EP3759081A1 EP 3759081 A1 EP3759081 A1 EP 3759081A1 EP 19760246 A EP19760246 A EP 19760246A EP 3759081 A1 EP3759081 A1 EP 3759081A1
Authority
EP
European Patent Office
Prior art keywords
formula
propiomazine
preparation
maleate
base
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.)
Pending
Application number
EP19760246.9A
Other languages
English (en)
French (fr)
Other versions
EP3759081A4 (de
Inventor
Kannasani RAVI KUMAR
Kasa Mallik Yadav
Mula SREENU
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
RA Chem Pharma Ltd
Original Assignee
RA Chem Pharma Ltd
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.)
Filing date
Publication date
Application filed by RA Chem Pharma Ltd filed Critical RA Chem Pharma Ltd
Publication of EP3759081A1 publication Critical patent/EP3759081A1/de
Publication of EP3759081A4 publication Critical patent/EP3759081A4/de
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
    • C07D279/18—[b, e]-condensed with two six-membered rings
    • C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
    • C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
    • C07D279/28—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom with other substituents attached to the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part

Definitions

  • the present invention relates to an improved process for the preparation of Propiomazine maleate. More particularly, the invention relates to a cost-effective process, which provides Propiomazine maleate of formula-I with high purity, which is free from isomeric impurity, specifically isopropiomazine.
  • Propiomazine maleate of formula-I is a phenothiazine derivative, chemically known as 1-[10-(2-dimethylaminopropyl)-10H-phenothiazin-2-yl]propan-1-one maleate.
  • Propiomazine is an antihistamine drug, which acts by blocking H1 receptors. It is used to treat insomnia, and to produce sleepiness or drowsiness and to relieve anxiety before or during surgery or other procedures and in combination with analgesics also during labor. Propiomazine is a derivative of Phenothiazine.
  • the main object of the present invention is to provide simple, cost-effective and industrially viable method for the preparation of Propiomazine maleate of formula-I on commercial scale.
  • the main aspect of the present invention is to provide an improved process for the preparation of Propiomazine maleate of formula-I.
  • the second aspect of the present invention is process for preparation of Propiomazine maleate with high purity which is free from isomeric impurity of formula-III.
  • the isomeric impurity produced during the preparation of Propiomazine base of formula II is controlled during the preparation of Propiomazine maleate.
  • the Propiomazine base of formula II is dissolved in alcoholic media to get a clear solution. Addition of maleic acid to the above clear solution produces Propiomazine maleate of formula-I which is free from isomeric impurity.
  • the present invention relates to an improved process for the preparation of Propiomazine maleate of formula-I and its purification from the undesired isomeric impurity. i.e., isopropiomazine of formula-III.
  • the first embodiment of the present invention is an improved process for the preparation of 1-[10-(2-dimethylaminopropyl)-10H-phenothiazin-2-yl]propan-1-one of formula-II, which comprises condensing 2-propionyl phenothiazine of formula –IV
  • Further embodiment of the present invention relates to process for preparation of Propiomazine maleate with high purity and free from isopropiomazine impurity of formula-III.
  • the isomeric impurity is controlled during the preparation of Propiomazine maleate.
  • the crude Propiomazine base obtained in the above condensation step contains isomeric impurity of 20-25%.
  • the Propiomazine base of formula II is dissolved in alcoholic media to get a clear solution. Addition of maleic acid to the above clear solution produces Propiomazine maleate of formula-I which is free from isomeric impurity.
  • the process is schematically represented as below:
  • the base used in condensation step is selected from potassium hydroxide, sodium hydroxide, potassium tertiary butoxide, preferably potassium hydroxide.
  • solvent used in condensation step is selected from the group comprising of toluene, xylene, preferably toluene.
  • alcoholic media used in purification step is selected from methanol, ethanol, isopropyl alcohol, preferably methanol.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP19760246.9A 2018-02-27 2019-02-18 Verbessertes verfahren zur herstellung von propiomazinmaleat Pending EP3759081A4 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201841007386 2018-02-27
PCT/IN2019/050128 WO2019167058A1 (en) 2018-02-27 2019-02-18 An improved process for the preparation of propiomazine maleate

Publications (2)

Publication Number Publication Date
EP3759081A1 true EP3759081A1 (de) 2021-01-06
EP3759081A4 EP3759081A4 (de) 2022-01-05

Family

ID=67804887

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19760246.9A Pending EP3759081A4 (de) 2018-02-27 2019-02-18 Verbessertes verfahren zur herstellung von propiomazinmaleat

Country Status (2)

Country Link
EP (1) EP3759081A4 (de)
WO (1) WO2019167058A1 (de)

Also Published As

Publication number Publication date
EP3759081A4 (de) 2022-01-05
WO2019167058A1 (en) 2019-09-06

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