SU1209026A3 - Способ получени арилциклобутилалкиламиновых соединений - Google Patents

Способ получени арилциклобутилалкиламиновых соединений Download PDF

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SU1209026A3
SU1209026A3 SU833647537A SU3647537A SU1209026A3 SU 1209026 A3 SU1209026 A3 SU 1209026A3 SU 833647537 A SU833647537 A SU 833647537A SU 3647537 A SU3647537 A SU 3647537A SU 1209026 A3 SU1209026 A3 SU 1209026A3
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hydroxy
phenyl
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Козлик Антонин
Хейс Веллс Велфред
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Дзе Бутс Компани Плс (Фирма)
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Description

имеют указанные зиаче -/ , 1чИЯ 5
В среде органического ;растворител 5 выбранного из метанола, этанола и пропан-2-ола, в присутствии боргид
Изобретение относитс  к органи- чаской химии,, а именно к способу полть чени  новых производных арилцик- лобутилалкнламиновых соединений э которые обладают антидепрессантной активностью и могут найти применение в медицине,
Цель изобретени  получение новых производных арилциклобутилалкил- аминовых соединенийJ которые могут найти применение в медицине в каче стве анти-Д.епрессантав
Пример 1 . Гидрохлори ; N - бензил-1 -(3 5 4--д,ихлорфенилцикло- бутилI этиламин,
1 Ацетил-i(3 9 4-дихлорфенил)цик- лобутан (4s86r) и бензиламин (2,2 мл) перемешивают при температуре 40 - 150 С в атмосфере азотэ. в течение 1 ч 30 мин. Метанол (500 мл) добавл ют в охлажденную реакционную смесь и в течение 10 мин добавл ют борог -щр-ид натри  (0,8 г). Далее смесь перемешивают при окружающей температуре 2 ч, а затем объем реак- ционной смеси снижаетс  на половину и.смесь сливаетс  в воду (300 ип) Водный раствор экстрагируют простьп эфиром и экстракт эфира сушат, а простой эфир удал ют выпариванием. Остаток подвергают дистилл ции (т.кип, , 182-186 С при Oj5 мь рт.ст) и дистилл т обрабатывают хлористым водородом в простом . эфире 5 в результате чего получают гидрохлорид N - 6ензил- 1 (3,4-дихлорфенил ) циклобу- тил этиламина . (т.пл,227-228 С) ,
П р и м е р ы 2 - .37, При помощи той же процедуры, что бьша описана в примере 1.получают соединени j приведенные в табл,1 и 2,
П р и м е р 38. 1-Ацетил--(354- дихлорфенил)циклобутан (5,0 г) добавл ют Б 2 й Пропоксиэтиланин (Ij9 г) и смесь перемешившот и
рида натри  или гтианборгидрида натри  при температуре от температуры окрул ающей среды до :.: температуры .кипени  реакционной смеси.
0
5
0
5
0
5
нагревают до 140-145 С в медленно продуваемом потоке азота, который используетс  дл  удалени  образующейс  воды, Нагревание продолжают в течение 20 ч в Смесь охлаждают и добавл ют суспензию борогидрида натри  (707 мг) в пропан--2-оле (60 мл) , а затем смесь Н-агревают до температуры дефлегмировани , котора  поддерживаетс  в течение 16 ч. Растворитель удал ют и остаток обрабатывают водой (150 мл) и продукт экстрагируют в простом эфире. Экстракт промывают водой .(10 X 75 мл), сушат, фильтруют и до авл ют раствор малеиновой кис- лоты(.2513 г) в простом эфире (100 мл), Смесь охлаждают, полученное в результате твердое веп ество рекристаллизуетс  из технического метилированного спирта, в результате чего получают малеат N-(2-nponoK- сиэтил) 1 -(3,4 дихлорфенил)1,икло- бутил этиламина (т,пл, 12-114 С),
Примеры 39-52, При помоши процедуры, аналогичной той, что использовалась в примере 38s были получены соединени , перечисленные в табЛо 3 и 4о
П р и м е р ы 53-66, При помощи той же процедуры, что была описана либо в примере , либо в примере 38, были получены соединени , приведенные в табл.5 и 6.
В таблицах обозначено:
-L и J.I (см,шапки таблиц) продолжительность (ч) и температура ( С), при. которых осуществл етс  реакци ., между кетоном и амином;
в графе Примечание :
(1)- продукт подвергалс  очистке при помощи жидкостной хроматографии под высоким давлением. Физические константы не определ лись;
(2)- температура точки кипени  свободного основани ;
3.
(3)- монохлоргидратна  соль;
(4)-дихлорх идратна  соль;
(5)-L- форма;
(6)-соль дималеата;
(7)-соль мономалеата;
(8)-моногидрат;
(9)-содержит 1,45 моль НС1 на моль;
(10)- полугидрат;
(11)- физические константы не определ лись, но структура соединени была проанализирована с использованием известных аналитических методов;
(12)- растворителем стадии вое- становлени  был этанол;
.(13) - растворителем стадии восстановлени  был метанол;
(14) растворителем стадии восстановлени  была смесь этанола и метанола ,
П р и м е р 67. При помощи процедуры , аналогичной той, что была описана в примере 38, получают гидро- . хлорид N -(2-метоксиэтил)-1- D(3,4- дихлорфенил) 11Йклобутил -2-метилпро- пиламина (т.пл. 158-16П°С),
П р и м е р 68. Смесь 1-ацетил- 1-(3,4-дихлорфенил)циклобутана (2,43 г) гидрохлорида глидинамида (2,21 г), порошкообразного гидрата окиси кали  (1,2 г) и цианоборогидри да натри  (1,5 г) в метаноле (20мл) перемешивают при 2 ч, затем еще 10 дней при окружающей темпера- Туре. Шесь охлаждают и добавл ют 5н.-раствор хлористо-водородной кислоты . Смесь затем подщелачивают, экстрагируют в простом эфире, промывают водой,сушат и выпаривают, в результате чего получают масло, которое раствор ют в простом эфире и добавл ют раствор малеиновой кислоты (1,0 г) в сухом простом эфире (100 мл), в результате чего масло, которое раствор етс  в ацетоне . Затем добавл ют простой эфир, в результате чего получают более твердое вещество, которое раствор ют в воде, подщелачивают и экстрагируют в простом эфире. Пропуска  га- зообразный хлористый водород через
09026
высушенный эфирный экстракт, получают гидрохлорид С 1(3,4-дихлорфенил (циклобутил этиламиноацег- амида (т.пл. 240-245 С), 5 Пример 69. Смесь 2-(4-меток- сифенокси)этиламина (7,0 г), 1-бу- тирил-1 -(3,4-дихлорфенил)циклобутана (10,8 г) и дихлорида дибутилтина (0,61 г) в сухом толуоле (20 мл) ремешивают и дефлегмируют 2ч, Толуол удал ют выпариванием и смесь нагревают до 175-1ВО С .erne в течение 7 ч. Смесь охлаждают, раствор ют в абсолютном этаноле (25 мл), затем до15 бавл ют в раствор борогидрид натри  (5 г) в этаноле ( 250 мл и смесь нагревают до температуры дефлегми- ровани , котора  поддерживаетс  в течение 2 ч. Этанол выпаривают и
20 смесь подкисл ют, подщелачивают и экстрагируют в простом эфире. Через высушенные экстракты пропускают хлористый водород, в результате чего получают липкое твердое вещество,
25 которое распредел етс  между простым эфиром и 5н. раствором гидрата окиси натри . Слой простого эфира промывают 5н. раствором хлористо-водородной кислоты, подщелачивают, экстра30 гируют в простом эфире и сушат. Добавл ют раствор малеиновой кислоты (Зг) в сухом простом эфире (300 мл), в результате чего получают.малеат (4-метоксифенокси) (3,4-дихлорфенил)циклобутил бутилами- на (т.пл. 164-1бб С).
П р и м е р 70. Смесь соединени  из примера 37 в форме его свободного основани  (3,2 г), 98%-ного раствора
д муравьиной кислоты (2 мл), 37-АО%-но- го водного раствора формальдегида (2,8 мл) и воды (0,28 мл) нагревают до температуры 90-95 С,которую поддерживают 18 ч.После охлаждени  добавл ют концентрированную кислоту (1 мл) и реакционную смесь вьтаривают до сухого состо ни . Остаток растирают с простым эфиром, в результате чего получают гидрат дигидрохлорида N -метил- К-(2-морфолиноэтил)-1- 1-(4-хлорфе- нил)циклобутил этиламина (т.пл, 225- 228°С, разл,).
5
О
СН,
хлорфенил- тио
Ииклогепт- 16 140 1-этил
Таблица 1
/О,1 мм рт,ст.
179-180/
/0,1 мм рт.ст.
(2)
0,2 мм рт.ст.
1 - ,™ CHNH(CHo)
I г u
3 ff
W Li
Me
CHNH(CH2)xW(CR2,yH6
44 2 2 0
OMe
Таблица2
ТаблицаЗ
1 10
119-120
(7) (12)
т
ctj
н
IS
R ю
« н.
f
1Л
-ir 1Л
in Ifl
t
Л
т
LO
о
ч
о
О
- см чО чо
п в
D tt) 3 IS
t;
lO
(fl
H
U3
eJ5
E
I
C)1209026
16

Claims (1)

  1. СПОСОБ ПОЛУЧЕНИЯ АРИЛЦИКЛ0БУТИЛАЛКИЛАМИНОВЫХ СОЕДИНЕНИЙ обшей формулы
    Ай-|— где - нормальный или разветвленный С-алкил или цикло— гексилметил;
    Аг - группа формулы -(СН2)Х~«-(СН 2)у где ад - кислород или сера, циклогексилиденовая или циклогексиленовая группа, или группа формулы
    -СК,Н4где R^-CV3 -алкил, гидрокси-, метокси- или бензильная группа;
    R4 -водород или Ct_3 -алкил;
    х - целое число от 0 до 4;
    у - целое· число от 0 до 4, при ус ловии, что когда ω - кислород или сера, х и у не равны 0;
    R2-гидрокси-, С(_4 -алкокси- ,φβ.ήокси- или цианогруппа, фенил, фенил, замещенный одним или двумя атомами галогена, галогенофенилтиогруппа, тиенил, пиридил, фурил, тетрагидрофурил, морфолино-, тиоморфолино-, пиперидино- или пирролидиногруппа, имидазолил, триазолил.или циклогептенил; ‘ .
    Аг - 2 -фторфенил, группа формулы
    А где R 5 - водород или галоген, или трифторметил;
    R6 - водород или галоген, фенил или метилтиогруппа или R5 и R6 вместе ,с атомами углерода, к которым они присоединены, образуют дополнительное бензольное кольцо, или Аг группа формулы или их фармацевтически приемлемых солей, отличающийся тем, что соединение общей формулы
    COTR tl где Аг и R( имеют указанные значения , подвергают взаимодействию с амином общей формулы h2nar2. где К^.и Аг имеют указанные значения s в среде органического^растворителя, выбранного из метанола, этанола и пропан-2-ола, в присутствии боргид рида натрия или цианборгидрида натрия при температуре от температуры окружающей среды до температуры кипения реакционной смеси.
SU833647537A 1982-09-30 1983-09-29 Способ получени арилциклобутилалкиламиновых соединений SU1209026A3 (ru)

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
RU2462451C2 (ru) * 2006-09-15 2012-09-27 Ривайва Фармасьютикалс, Инк. Способ получения, способы применения и композиции циклоалкилметиламинов
RU2642074C2 (ru) * 2011-12-30 2018-01-24 Ревива Фармасьютикалс, Инк. Композиции, синтез и способы применения производных фенилциклоалкилметиламина

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU576307B2 (en) * 1982-09-24 1988-08-25 Commonwealth Scientific And Industrial Research Organisation Arthropodicidal compounds
GB8501192D0 (en) * 1985-01-17 1985-02-20 Boots Co Plc Therapeutic agents
EP0213080B1 (de) * 1985-08-27 1992-05-20 Ciba-Geigy Ag Hydropyridin-Derivate
GB8531071D0 (en) * 1985-12-17 1986-01-29 Boots Co Plc Therapeutic compound
GB8704777D0 (en) * 1987-02-28 1987-04-01 Boots Co Plc Medical treatment
GB9309749D0 (en) * 1993-05-12 1993-06-23 Boots Co Plc Therapeutic agents
GB9915617D0 (en) 1999-07-05 1999-09-01 Knoll Ag Therapeutic agents
ATE469875T1 (de) * 2002-03-13 2010-06-15 Schering Corp Nk1-antagonisten
WO2012003501A2 (en) 2010-07-02 2012-01-05 Reviva Pharmaceuticals, Inc. Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1124485B (de) * 1960-02-12 1962-03-01 Hoechst Ag Verfahren zur Herstellung von analeptisch wirksamen Phenylcycloalkylmethylaminen
SE7600674L (sv) * 1975-02-05 1976-08-06 Rohm & Haas Fungicider
IE52768B1 (en) * 1981-04-06 1988-02-17 Boots Co Ltd 1-arylcyclobutylalkylamine compounds useful as therapeutic agents
ZA821577B (en) * 1981-04-06 1983-03-30 Boots Co Plc Therapeutic agents
US4443449A (en) * 1981-04-06 1984-04-17 The Boots Company Limited Arylcyclobutylalkylamines and anti-depression composition and methods using same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Вейганд-Хильгетаг. Методы эксперимента в органической химии. Под. ред.проф.Н.Н. Суворова. Пер.с нем. К.: Хими , 1968, с.529 *

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Publication number Priority date Publication date Assignee Title
RU2462451C2 (ru) * 2006-09-15 2012-09-27 Ривайва Фармасьютикалс, Инк. Способ получения, способы применения и композиции циклоалкилметиламинов
RU2642074C2 (ru) * 2011-12-30 2018-01-24 Ревива Фармасьютикалс, Инк. Композиции, синтез и способы применения производных фенилциклоалкилметиламина

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