SU850001A3 - Способ получени производных пролина - Google Patents

Способ получени производных пролина Download PDF

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Publication number
SU850001A3
SU850001A3 SU782595500A SU2595500A SU850001A3 SU 850001 A3 SU850001 A3 SU 850001A3 SU 782595500 A SU782595500 A SU 782595500A SU 2595500 A SU2595500 A SU 2595500A SU 850001 A3 SU850001 A3 SU 850001A3
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USSR - Soviet Union
Prior art keywords
salts
proline
general formula
salt
organic
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SU782595500A
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English (en)
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Энджэл Ондетти Мигуэль
Вэйн Кашмэн Дэвид
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Е.Р.Сквибб Энд Санз, Инк. (Фирма)
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/15—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen
    • C07C53/19—Acids containing three or more carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic 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
    • C07D207/04—Heterocyclic 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
    • C07D207/10—Heterocyclic 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Description

(54) СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ ПРОЛИНА

Claims (2)

  1. Изобретение относитс  к получени новых производных пролина, которые могут найти применение в медицине. . Известна реакци  взаимодействи  аминов с лактонами . Цель изобретени  - разработка на основе известного метода способа по лучени  новых соединений, обладающих ценными фармакологическими свой ствами. Поставленна  цель достигаетс  те что согласно способу получени  производных пролина общей формулы . а HS-CH2-tHi-CQ где R - алкил с 1-4С или оксигрупп соединение общей формулы HNL СОЙ, В где R имеет вышеуказанные значени  подвергают взаимодействию с тиолакт ном общей формулы в среде органического растворител . Сложный эфир I I ацилируют тиолактоном, например р -пропиотиолак- тоном, с6 -метил-)-пропиотиолактоном или другим подобным соединением,реакцию можно осуществл ть в безводном растворителе, таком как тетрагидрофуран , хлорид метилена или подобном соединении в интервале температур от до комнатной. Группа, соответствующа  сложному эфиру, может быть удалена путем обработки анизолом и трифторуксусной кислоты при комнатной температуре. Полученные соединени  образуют основные соли с различными органическими и неорганическими основани ми. Такие соли включают соли аммони , соли щелочных металлов, подобные сол м натри  и кали  (которые  вл ютс  предпочтительными) соли щелочноземельных металлов, подобные сол м каль.ци  и магни , соли с органическими основани ми , например дициклогексиламинова  соль, соли бензатина, N-метил-О- , -глюкамина, гидрабамина, соли с аминокислотами , подобные аргинину, лизину и подобным им соединени м. Предпочтительными  вл ютс  нетоксичные, физиологически совместимые соли, хот  могут примен тьс  также и другие соли , например при изолировании или очистке продукта, как показано в примерах , относ щихс  к соли дициклогексиамина . Соли получают обычным способом путем реакции продукта в форме свободной кислоты с одним или несколькими эквивалентами соответствующего основани , обеспечивающими получение требуемого катиона в растворителе или в среде, в которой соль  вл етс  нерастворимой, либо в воде с удалением воды путем сушки вымораживанием . Путем нейтрализации соли нерастворимой кислотой, подобной катионообменной смоле в водородной форме (.например в смоле полистироль ной .сульфокислоты, подобной Довекс (Ооwex 50) и/или водным раствором кислоты и экстрагированием органическим растворителем, например этилацетатом дихлорметаном или подобным им соединением , можно получить свободную кислоту и, если имеетс  необходимость .образовать другую соль. Пример 1. 1-(3-Меркаптопропаноил )-4-пролин трет-бутиловый эфир К раствору 4-пролин трет-бутилового эфира (3,42 г) в сухом тетрагидро фуране (10 мп), охлажденном в лед ной бане, добавл ют пропиотиолактон (1,76 г). После выдерживани  в течение 5 мин в лед ной бане и в течение трех часов при комнатной температуре реакционную смесь разбавл ют этилацетатом (200 мп) и промывают 5%-ным бисульфатом кали  и водой. Органический слой высушивают над сульфатом магни  и концентрируют в вакууме до получени  сухого вещества. Полученны в осадке 1-(3-меркаптопропаноил)-4-прсэлин трет-бутиловый эфир кристалл зуют из смеси эфир-гексан, при этом , выход продукта составл ет 3,7 г,температура плавлени  57-58 С. Пример
  2. 2. Использу  вместе 4-пролин трет-бутилового сложного эфира, примен емого в примере 1, 4-пролин получают 1/-3-меркаптопропаноил -4-пролин с т.гш. 68-70 С после перекристаллизации продукта реакции из смесей этилацетата и гексана. Формула изобретени  Способ получени  производных пролина общей формулы 1 if СО-ЦL coR HS- CHj- СИ где R - алкил с 1-4С или оксигруппа, отличающийс  тем, что соединение общей формулы II ННi-i где R имеет вышеуказанные значени , подвергают взаимодействию с тиолактоном общей формулы III в среде органического растворител . Источники информации, прин тые во внимание при экспертизе 1. Бюлер К.и Пирсон Д. Органические синтезы. Мир, 1973, ч. 2, с.. 391.
SU782595500A 1976-02-13 1978-03-31 Способ получени производных пролина SU850001A3 (ru)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US05/657,792 US4046889A (en) 1976-02-13 1976-02-13 Azetidine-2-carboxylic acid derivatives

Publications (1)

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SU850001A3 true SU850001A3 (ru) 1981-07-23

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SU782595499A SU845775A3 (ru) 1976-02-13 1978-03-31 Способ получени производныхпРОлиНА
SU782595500A SU850001A3 (ru) 1976-02-13 1978-03-31 Способ получени производных пролина

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Country Status (8)

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US (2) US4046889A (ru)
JP (3) JPS6059226B2 (ru)
BE (1) BE851361A (ru)
CS (1) CS207578B2 (ru)
DD (2) DD283999A5 (ru)
HU (1) HU185576B (ru)
SU (2) SU845775A3 (ru)
ZA (1) ZA77313B (ru)

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JPS58189158A (ja) 1983-11-04
BE851361A (fr) 1977-08-11
US4046889A (en) 1977-09-06
HU185576B (en) 1985-02-28
ZA77313B (en) 1977-11-30
SU845775A3 (ru) 1981-07-07
JPS6056705B2 (ja) 1985-12-11
JPS6059226B2 (ja) 1985-12-24
DD283998A5 (de) 1990-10-31
US4154840A (en) 1979-05-15

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