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SU507225A3 - Production method - propionyl-4-hydroxyproline or its salts - Google Patents

Production method - propionyl-4-hydroxyproline or its salts

Info

Publication number
SU507225A3
SU507225A3 SU1972265A SU1972265A SU507225A3 SU 507225 A3 SU507225 A3 SU 507225A3 SU 1972265 A SU1972265 A SU 1972265A SU 1972265 A SU1972265 A SU 1972265A SU 507225 A3 SU507225 A3 SU 507225A3
Authority
SU
USSR - Soviet Union
Prior art keywords
hydroxyproline
propionyl
salts
production method
salt
Prior art date
Application number
SU1972265A
Other languages
Russian (ru)
Inventor
Фарж Даниель
Наум Мессер Майер
Мутоннье Клод
Original Assignee
Рон-Пуленк С.А. (Фирма)
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 Рон-Пуленк С.А. (Фирма) filed Critical Рон-Пуленк С.А. (Фирма)
Application granted granted Critical
Publication of SU507225A3 publication Critical patent/SU507225A3/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D207/16Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Rheumatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pyrrole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)

Description

СПОСОБ ПОЛУЧЕНИЯ L - N -ПРОПИОНИЛ-4-ОКСИПРОЛИНА METHOD OF OBTAINING L - N-PROPIONIL-4-OXIPROLINE

(54) ИЛИ ЕГО СОЛЕЙ(54) OR HIS SALTS

Изобретение относитс  к способу по лучени  нового ПРОИЗВОДНОГО; пролина, которое может найти применение в фармацевтической проквлиленности. Известен способ получени  N-ацильиых производных взаимодействием амина с ангидридном карбоновой кислоты в рас творе той же кислоты. Использу  известный способ примени тельно к Ъ -4-оксипролину, получают неописанный ранее L - N -пропионил4-оксипролин , обладающий иённными фар макологическими свойствами. Согласно изобретению предлагаетс  способ получени  L - N -пропионил-4оксипропилина , заключающийс  в том, что L -4-оксипролин подвергают взаимодействию со смесью пропионового аИгидрида и пропионовой кислоты и целевой продукт выдел ют в виде основани  металлической соли или соли с азотсосодержащим основанием. Процесс согласно изобретению обычно провод т при 25-80с. Целевой продукт может быть в случае необходимости очищен известными физическими методами, например хроматографией или перекристаллизацией, или химическими методами, например переведением в металлическую соль, которую сначала перекристаллизовывают , а затем при подкислении перевод т в основание. L - ТЧ -пропионил-4-оксипролин может быть превращен известными способАми в металлическую соль или соль азотсодержащего основани  в подход щем растворителе, например спирте, эфире кетонах или воде. Образовавша с  соль выпадает в осадок, который отфильтровывают или декантируют |п6сле концент-рировани  раствора. В качестве оснований используют гидраты окисей щелочных или щелочноземельных металлов, аммиак или амины. Строение L - N -пропионил-4-оксипролина однозначно доказано ИК-и ЯМР спектрами. ll м е р. К смеси 110 г I. -4оксипролина и 400 мл пропионовой кислоты , нагретой до 50с, прибавл ют по капл м раствор 119,5 г пропионозото ангидрида в 100 мл пропионовой кислоты в течение 30 мин. Реакционную массу перемешивают 10 мин при 50с. Доб1авл ют 800 мл диизопропилового эфира , при этом выдел ют кристаллы продукта . Реакционную смесь охлаждают до 15 С Лприбавл ют еще 300 мл диизопропилового эфира. Кристаллический осадок отфильтровывают, промывают 600 мл диизспропилового эфира. Получают 129 г продукта ст. пл. 138 С. После перекристаллизации из 310 ьл ацетанитрила получают 118 rt -N п ропионил-4-оксипролина с т. пл. 139С,This invention relates to a process for producing a new DERIVATIVE; proline, which can be used in pharmaceutical fertility. A known method for producing N-acyl derivatives by reacting an amine with a carboxylic anhydride in a solution of the same acid. Using the known method applicable to b-4-hydroxyproline, L-N-propionyl-4-hydroxyproline, which has not been described previously, is obtained, which possesses macrophilic properties of headlights. According to the invention, a method for producing L-N-propionyl-4-oxypropylin is proposed, namely, L-4-hydroxyproline is reacted with a mixture of propionic aHydride and propionic acid and the target product is isolated as a base metal salt or salt with a nitrogen-containing base. The process according to the invention is usually carried out at 25-80 seconds. The desired product can, if necessary, be purified by known physical methods, for example by chromatography or recrystallization, or by chemical methods, for example by conversion into a metal salt, which is first recrystallized and then transferred to the base upon acidification. L-PM-propionyl-4-hydroxyproline can be converted by known methods to a metal salt or a salt of a nitrogen-containing base in a suitable solvent, for example, alcohol, ketone ester or water. The resulting salt precipitates, which is filtered or decanted | after concentration of the solution. The bases used are alkali or alkaline earth metal oxide hydrates, ammonia or amines. The structure of L - N-propionyl-4-hydroxyproline is unequivocally proven by IR and NMR spectra. ll merid. To a mixture of 110 g of I. -4-oxyproline and 400 ml of propionic acid heated to 50 s, a solution of 119.5 g of propionic acid anhydride in 100 ml of propionic acid is added dropwise over 30 minutes. The reaction mass is stirred for 10 min at 50 s. 800 ml of diisopropyl ether are added, and product crystals are isolated. The reaction mixture is cooled to 15 ° C. Another 300 ml of diisopropyl ether is added. The crystalline precipitate is filtered off, washed with 600 ml of diisopropyl ether. 129 g of product are obtained. square 138 C. After recrystallization from 310 ml of acetanitrile, 118 rt -N p-pionionyl-4-hydroxyproline with m.p. 139С,

io dtl i-U4 t l. 1, вода).io dtl i-U4 t l. 1, water).

Claims (1)

Формула изобретени  Способ получени  Ь - N -пропионил4-оксипролина или его солей, отличающийс  тем, что L -4-оксипролин подвергают взаимодействию со смесью пропионового ангидрида и пропионовой кислоты с последующим выделением целевого продукта в виде основани  или соли известными приемами.Claims for the preparation of L-N-propionyl 4-hydroxyproline or its salts, characterized in that the L-4-hydroxyproline is reacted with a mixture of propionic anhydride and propionic acid, followed by isolation of the desired product as a base or salt by known methods.
SU1972265A 1972-11-23 1973-11-22 Production method - propionyl-4-hydroxyproline or its salts SU507225A3 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR7241639A FR2207702B1 (en) 1972-11-23 1972-11-23

Publications (1)

Publication Number Publication Date
SU507225A3 true SU507225A3 (en) 1976-03-15

Family

ID=9107588

Family Applications (1)

Application Number Title Priority Date Filing Date
SU1972265A SU507225A3 (en) 1972-11-23 1973-11-22 Production method - propionyl-4-hydroxyproline or its salts

Country Status (19)

Country Link
JP (1) JPS504066A (en)
AR (1) AR199319A1 (en)
AU (1) AU473116B2 (en)
BE (1) BE807684A (en)
CA (1) CA1001635A (en)
CH (1) CH576958A5 (en)
DD (1) DD107455A5 (en)
DE (1) DE2358470A1 (en)
ES (1) ES420780A1 (en)
FR (1) FR2207702B1 (en)
GB (1) GB1397675A (en)
HU (1) HU166917B (en)
IL (1) IL43684A (en)
LU (1) LU68846A1 (en)
NL (1) NL7315685A (en)
OA (1) OA04505A (en)
SE (1) SE382453B (en)
SU (1) SU507225A3 (en)
ZA (1) ZA738874B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1281288C (en) * 1984-11-05 1991-03-12 Wilhelm Hoerrmann Tumor therapy
JPS63218621A (en) * 1987-03-09 1988-09-12 Kazuoki Tsuchiya Composition for prevention and remedy of obesity
WO2006046690A1 (en) * 2004-10-28 2006-05-04 Kyowa Hakko Kogyo Co., Ltd. Composition for oral cavity

Also Published As

Publication number Publication date
CA1001635A (en) 1976-12-14
CH576958A5 (en) 1976-06-30
GB1397675A (en) 1975-06-18
IL43684A (en) 1976-06-30
AR199319A1 (en) 1974-08-23
JPS504066A (en) 1975-01-16
ZA738874B (en) 1974-10-30
IL43684A0 (en) 1974-03-14
OA04505A (en) 1980-03-30
DD107455A5 (en) 1974-08-05
ES420780A1 (en) 1976-04-01
AU473116B2 (en) 1976-06-10
NL7315685A (en) 1974-05-27
FR2207702B1 (en) 1975-11-28
AU6277173A (en) 1975-05-22
FR2207702A1 (en) 1974-06-21
DE2358470A1 (en) 1974-05-30
BE807684A (en) 1974-05-22
LU68846A1 (en) 1974-06-21
SE382453B (en) 1976-02-02
HU166917B (en) 1975-06-28

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