SU1250170A3 - Способ получени дихлоргидрата пирбутерола - Google Patents
Способ получени дихлоргидрата пирбутерола Download PDFInfo
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- SU1250170A3 SU1250170A3 SU833534854A SU3534854A SU1250170A3 SU 1250170 A3 SU1250170 A3 SU 1250170A3 SU 833534854 A SU833534854 A SU 833534854A SU 3534854 A SU3534854 A SU 3534854A SU 1250170 A3 SU1250170 A3 SU 1250170A3
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- formula
- compound
- methyl
- hydrogen
- acetoxy
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
см
1
Изобретение относитс к способу получени дихлорпздрата пирЗутерола который обладает бронхорасшир ю-. щей активностью.
Цель изобретени - упрощение процесса.
Пример 1. З-Аце токси-2- -метил-6- 1-ацетокси-2-(Н-трет- -бутилацетамидо)-этил пиридин.
К суспензии 2-(1-гидрокси-2- -трет-бутиламиноэтил)-5-гидрокси- -6-метилпиридина дигидрохлорида (7,70 г 0,026 моль) в 300 мл этил- ацетата и 7,7 мл триэтиламина добавл ют 10,8 мл уксусного ангидрида и раствор нагревают при температуре кипени с обратным холодильником в течение 30 ч. К реакционной смеси добавл ют еще 5 мл уксусного ангидрида и нагревание продолжают в течение 24 ч, затем охлаждают до комнатной температуры. Реакционную смесь выливают в водный раствор бикарбоната натри (100 г NaHCOj в 700 мл Н20) и:результирующую смесь перемешивают в течение 1 ч. Отдел ют этилацетатный слой, промывают водным бикарбонатом натри , затем водой и осушают над сульфатом магни . Упаривание осушенного этил- ацетатного раствора в вакууме дает 3-а:цетокси-2-метил-6- l -ацетокси- -2 (Ы-трет-бу тилацетамидо)-зтил пиридин , в количестве 6,0 г (66%), т.пл. 124,6-127,5 С.
Найдено,%: С 61,93; Н 7,39; N 8,44.
C,8H,eN,Oj
Вычислено,% N 8,09.
Пример
С 61,70; Н 7,48;
.. г - - - S- 2. N-Оксид-З-ацеток си-2-метил-б-и-ацетокси-2-(N-трет- бутилацетамидо)этил пиридина.
Раствор 3-ацетокси-2-метил-6- - -|1-ацетокси-2-(Ы-трет-бутилацетамидо )этил пиридина (5,50 г, О,О 57 моль) и м-хлорпербензойной кислоты (технически чистой - 85%, 3,90 г 0,0192 моль) в 150 мл хлороформа перемешивают при комнатной температуре в течение 24 ч. После промывани реакционной смеси двум порци ми водного раствора бикарбоната натри , осушенный (MgS04) хлороформный раствор упаривают с получением 2,9 г (50%) З-ацетокси-2-ме- тил-6- 1-ацетокси-2-(Н-трет-бутил- ацетамидо)этил пиридин-Н-оксида,
10
15
20
25
250Г701
т.пл. 113-116 с (после перекристаллизации из эфира).
Найдено, %: С 59,25; Н 7,08; N 8,1-4.
5 C,H,,N,Oe . .
I Вычислено,%: С 59,ОО; Н 7,15, N 7,65. . . . П р и, м, е р 3. З-Ацетокси-2- -ацетоксиметил-6 -1-ацетокси-(Ы- -трет-бутилацетамидо)этил пиридин. Раствор 1,0 г (0,0027 моль) N- -ацвтокси-2-метил-6- 1-ацетокси-2- -(Ы-трет-бутш1ацетамидо)этил пнри- дйн-Ы-оксида в 10 мл уксусного ангидрида нагревают при температуре кипени с обратным холодильником в течение 2,5 ч, затем оставл ют охлаждатьс до комнатной температуры и перемешивают при этой температуре в течение ночи. Затем реакционную смесь выливают в двухфазную смесь этилацетата и водного бикарбоната натри и перемешивают в течение 1 ч. Органический слой отдел ют, осушают над безводным сульфатом магни , фильтруют и упаривают до сухого остатка в вакууме с получением коричневого масла,которое очищают хроматографированием в колонке на силикагеле с ислользо- ванием эфира в качестве элюента, получа 300 мг (27%) целевого продукта , т.пл. 60-64 с.
Найдено, %: С 59,02; Н 6,83;
35 N 7,30.
Ъы ислено,7,; N 6,86.
Пример
.Q гидрохлорид.
Раствор 2,0 г (0,005 моль) 2- -ацетоксиметил-З-ацетокси-6-(1- -ацеток си-2К-аце тил-трет-бутилами- ноэтил)пиридина в 50 мл метанола, содержащего 1 мл концентрированной хлористоводородной кислоты, нагревают с обратным холодильником в течение 12 ч. Растворители удал ют в вакууме и остаток перекристалли- зовьгеают из этилацетата с получением пирбутерола дигидрохлорида (900 мг 58%), т.пл. 172-175°С (с разложением), ЯМР-спектр и ТСХ Et OAZrCHjOHrEt NH (6:3:1) идентичны пирбутеролу. Продолжительное нагре55 вание ведет к образованию побочного 2-гидроксиметил-3-гидрокси-6-(1- -гидрокси-2-миноэтил)пиридина, т.пл. 184-186°С (с разложением).
30
С 58,81; Н 6,91; 4. Пирбутерола ди45
50
Claims (1)
- . СПОСОБ ПОЛУЧЕНИЯ ДИХЛОРГИДРАТА ПИРБУТЕРОЛА исходя из производного пиридина, отличающийся тем, что, с целью упрощения процесса, в качестве произ водного пиридина используют соединение формулы .СН3СООу?\I ососщ ^0СНг которое нагревают в уксусном ангидриде с последующим кислотным гидролизом соляной кислотой образовавшегося соединения формулыСН3СООу^.СНзСОоАД^-—N_x ОСОСН3 <кн3 n9>SU 1250170 А 5
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23292381A | 1981-02-09 | 1981-02-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SU1250170A3 true SU1250170A3 (ru) | 1986-08-07 |
Family
ID=22875140
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU823392299A SU1194273A3 (ru) | 1981-02-09 | 1982-02-03 | Способ получени пирбутерола или его аналогов |
| SU833534107A SU1240354A3 (ru) | 1981-02-09 | 1983-01-05 | Способ получени дигидрохлорида пирбутерола |
| SU833534854A SU1250170A3 (ru) | 1981-02-09 | 1983-01-05 | Способ получени дихлоргидрата пирбутерола |
| SU833535711A SU1217253A3 (ru) | 1981-02-09 | 1983-01-05 | Способ получени пирбутерола дигидрохлорида |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU823392299A SU1194273A3 (ru) | 1981-02-09 | 1982-02-03 | Способ получени пирбутерола или его аналогов |
| SU833534107A SU1240354A3 (ru) | 1981-02-09 | 1983-01-05 | Способ получени дигидрохлорида пирбутерола |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU833535711A SU1217253A3 (ru) | 1981-02-09 | 1983-01-05 | Способ получени пирбутерола дигидрохлорида |
Country Status (26)
| Country | Link |
|---|---|
| EP (4) | EP0058072A3 (ru) |
| JP (4) | JPS57150665A (ru) |
| KR (1) | KR860000623B1 (ru) |
| AR (4) | AR231439A1 (ru) |
| AT (2) | ATE20882T1 (ru) |
| AU (1) | AU530826B2 (ru) |
| CA (1) | CA1179677A (ru) |
| CS (1) | CS229678B2 (ru) |
| DD (2) | DD210034A5 (ru) |
| DE (2) | DE3272793D1 (ru) |
| DK (1) | DK157541C (ru) |
| EG (1) | EG16242A (ru) |
| ES (4) | ES8305721A1 (ru) |
| FI (1) | FI820396A7 (ru) |
| GR (1) | GR75867B (ru) |
| GT (1) | GT198273686A (ru) |
| IE (2) | IE52326B1 (ru) |
| IL (1) | IL64954A (ru) |
| NO (4) | NO820371L (ru) |
| NZ (1) | NZ199646A (ru) |
| PH (4) | PH20622A (ru) |
| PL (4) | PL130918B1 (ru) |
| PT (1) | PT74397B (ru) |
| SU (4) | SU1194273A3 (ru) |
| YU (3) | YU42756B (ru) |
| ZA (1) | ZA82778B (ru) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3615293A1 (de) * | 1986-05-06 | 1987-11-12 | Bayer Ag | Verwendung von heteroarylethylaminen zur leistungsfoerderung bei tieren, heteroarylethylamine und verfahren zu ihrer herstellung |
| DE19845402B4 (de) * | 1998-10-02 | 2005-04-07 | Aventis Pharma Deutschland Gmbh | Mit Heterocyclen substituierte Propanolaminderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| DE19845405C2 (de) * | 1998-10-02 | 2000-07-13 | Aventis Pharma Gmbh | Arylsubstituierte Propanolaminderivate und deren Verwendung |
| DE19845406C2 (de) * | 1998-10-02 | 2001-10-18 | Aventis Pharma Gmbh | Substituierte 1,3-Diaryl-2-pyridin-2-yl-3-(pyridin-2-ylamino)- propanolderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3700681A (en) * | 1971-02-16 | 1972-10-24 | Pfizer | 2-hydroxymethyl-3-hydroxy-6-(1-hydroxy-2-aminoethyl)pyridines |
| BE795937A (fr) * | 1972-03-01 | 1973-08-27 | Pepro | Procede d'hydroxymethylation d'une 3-hydroxy-pyridine substituee |
| AR207639A1 (es) * | 1973-12-26 | 1976-10-22 | Pfizer | Un procedimiento para preparar pirido (3,2-d)1,3-dioxin-6-epoxietanos y compuestos intermediarios desprovistos de actividad terapeutica |
| US4031108A (en) * | 1974-10-09 | 1977-06-21 | Pfizer Inc. | 2-Hydroxymethyl-3-benzyloxypyridine-6-epoxyethane |
| US3952101A (en) * | 1975-04-14 | 1976-04-20 | Smithkline Corporation | α-Amino methyl-5-hydroxy-2-pyridinemethanols |
-
1982
- 1982-02-03 SU SU823392299A patent/SU1194273A3/ru active
- 1982-02-04 NZ NZ199646A patent/NZ199646A/en unknown
- 1982-02-04 CS CS82781A patent/CS229678B2/cs unknown
- 1982-02-05 GR GR67223A patent/GR75867B/el unknown
- 1982-02-05 AR AR288347A patent/AR231439A1/es active
- 1982-02-05 GT GT198273686A patent/GT198273686A/es unknown
- 1982-02-08 IE IE275/82A patent/IE52326B1/en not_active IP Right Cessation
- 1982-02-08 DE DE8282300602T patent/DE3272793D1/de not_active Expired
- 1982-02-08 YU YU266/82A patent/YU42756B/xx unknown
- 1982-02-08 DE DE8282300604T patent/DE3272061D1/de not_active Expired
- 1982-02-08 DD DD82253605A patent/DD210034A5/de unknown
- 1982-02-08 DK DK052182A patent/DK157541C/da not_active IP Right Cessation
- 1982-02-08 NO NO820371A patent/NO820371L/no unknown
- 1982-02-08 JP JP57018693A patent/JPS57150665A/ja active Granted
- 1982-02-08 EP EP82300605A patent/EP0058072A3/en not_active Withdrawn
- 1982-02-08 AU AU80271/82A patent/AU530826B2/en not_active Expired
- 1982-02-08 EP EP82300603A patent/EP0058070A3/en not_active Withdrawn
- 1982-02-08 CA CA000395768A patent/CA1179677A/en not_active Expired
- 1982-02-08 AT AT82300604T patent/ATE20882T1/de active
- 1982-02-08 DD DD82237264A patent/DD202544A5/de not_active IP Right Cessation
- 1982-02-08 IE IE273/82A patent/IE52325B1/en not_active IP Right Cessation
- 1982-02-08 FI FI820396A patent/FI820396A7/fi not_active Application Discontinuation
- 1982-02-08 AT AT82300602T patent/ATE21691T1/de active
- 1982-02-08 EP EP82300604A patent/EP0058071B1/en not_active Expired
- 1982-02-08 KR KR8200528A patent/KR860000623B1/ko not_active Expired
- 1982-02-08 ES ES509430A patent/ES8305721A1/es not_active Expired
- 1982-02-08 ZA ZA82778A patent/ZA82778B/xx unknown
- 1982-02-08 EP EP82300602A patent/EP0058069B1/en not_active Expired
- 1982-02-08 PT PT74397A patent/PT74397B/pt unknown
- 1982-02-09 EG EG60/82A patent/EG16242A/xx active
- 1982-02-09 IL IL64954A patent/IL64954A/xx active IP Right Revival
- 1982-02-09 PH PH26843A patent/PH20622A/en unknown
- 1982-02-09 PL PL1982239428A patent/PL130918B1/pl unknown
- 1982-02-09 PL PL1982235000A patent/PL130580B1/pl unknown
- 1982-02-09 PL PL1982239427A patent/PL130917B1/pl unknown
- 1982-02-09 PL PL1982239426A patent/PL130678B1/pl unknown
- 1982-11-17 AR AR291329A patent/AR229712A1/es active
- 1982-11-17 AR AR291327A patent/AR229373A1/es active
- 1982-11-17 AR AR291328A patent/AR229374A1/es active
- 1982-12-20 NO NO824275A patent/NO824275L/no unknown
- 1982-12-20 NO NO824273A patent/NO824273L/no unknown
- 1982-12-20 NO NO824274A patent/NO824274L/no unknown
-
1983
- 1983-01-05 SU SU833534107A patent/SU1240354A3/ru active
- 1983-01-05 SU SU833534854A patent/SU1250170A3/ru active
- 1983-01-05 SU SU833535711A patent/SU1217253A3/ru active
- 1983-01-13 ES ES518973A patent/ES518973A0/es active Granted
- 1983-01-13 ES ES518972A patent/ES8403111A1/es not_active Expired
- 1983-01-13 ES ES518971A patent/ES518971A0/es active Granted
- 1983-10-19 PH PH29714A patent/PH19164A/en unknown
- 1983-10-19 PH PH29712A patent/PH20292A/en unknown
- 1983-10-19 PH PH29713A patent/PH19167A/en unknown
-
1984
- 1984-11-28 YU YU2019/84A patent/YU42908B/xx unknown
- 1984-11-28 YU YU2018/84A patent/YU43389B/xx unknown
-
1985
- 1985-01-23 JP JP60010724A patent/JPS6059231B2/ja not_active Expired
- 1985-01-23 JP JP60010723A patent/JPS6059911B2/ja not_active Expired
- 1985-10-09 JP JP60225922A patent/JPS6193164A/ja active Granted
Non-Patent Citations (1)
| Title |
|---|
| Патент US № 3948819, кл. 260-296 Р, 1976. * |
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