DE1695826A1 - 1,4-Dihydro-4-(2-trifluormethylphenyl)-pyridine und Verfahren zu ihrer Herstellung - Google Patents

1,4-Dihydro-4-(2-trifluormethylphenyl)-pyridine und Verfahren zu ihrer Herstellung

Info

Publication number
DE1695826A1
DE1695826A1 DE1968S0113954 DES0113954A DE1695826A1 DE 1695826 A1 DE1695826 A1 DE 1695826A1 DE 1968S0113954 DE1968S0113954 DE 1968S0113954 DE S0113954 A DES0113954 A DE S0113954A DE 1695826 A1 DE1695826 A1 DE 1695826A1
Authority
DE
Germany
Prior art keywords
dihydro
general formula
trifluoromethylphenyl
coor
hol
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.)
Granted
Application number
DE1968S0113954
Other languages
English (en)
Other versions
DE1695826B2 (de
DE1695826C3 (de
Inventor
Tedeschi Ralph Earl
Bernard Loev
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.)
Smith Kline and French Laboratories Ltd
Original Assignee
Smith Kline and French Laboratories 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 Smith Kline and French Laboratories Ltd filed Critical Smith Kline and French Laboratories Ltd
Publication of DE1695826A1 publication Critical patent/DE1695826A1/de
Publication of DE1695826B2 publication Critical patent/DE1695826B2/de
Application granted granted Critical
Publication of DE1695826C3 publication Critical patent/DE1695826C3/de
Expired legal-status Critical Current

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Classifications

    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/02—Preparation by ring-closure or hydrogenation
    • 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
    • C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
    • C07D211/84—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 two 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 directly attached to ring carbon atoms
    • C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)

Description

DR. ELISABETH JUNG. DR. VOLKER VOSSIUS. DIPL.-ING. GERHARD COLDEWEY PATENTANWÄLTE
. MONCHIN 23 . MEQE88TRAtSEH . TILEFONKMiT · TILIQHAMM-ADiIE88E: INVENT/MDNffHtN
D 125 (vo/su/Gü) t 1,FEB 1968
loev-R.Tedeschi Case 1-P *·. rto. ww
Smith Kline & French laboratories Philadelphia, Pennsylvania, V.St.λ.
1,4-Dihydro-4- (2-trifluormethylphenyl)-pyridine und Verfahren zu ihrer Herstellung
Priorität» 7. Februar 1967, V.St.A. Anaeidβ-Nr.: 614 393
Die vorliegende Erfindung betrifft neue l,4-Dihydro-4-(2-trifluoraethylphenyl)-pyridine der allgemeinen Formel I
COOR2
Rl
in der R^ und R2 Alkylreate mit 1 bis 6 Kohlenstoffatomen bedeuten.
Die erfindungagemäQen Verbindungen sind Arzneimittel, und sie besitzen blutdrucksenkende Wirkung. Eine bevorzugte Verbindung der allgemeinen Formel I ist 3,5-Dicarbäthoxy-
109820/2203
l-4~äihydro-2,6-dimethyl-4~ (2~trifluormethyl phenyl )-pyridin, das bei oraler Verabreichung eine besondere kräftige blutdrucksengende Wirkung von verhältnismäßig langer Sauer selgt
Die Erfindung betrifft ferner ein Verfahren sur Herstellung der Verbindungen der allgemeinen Formel I» das dadurch gekennzeichnet ist, daß man etwa 1 Moläquivalent o-Trifluormethylbenealdehyd
a) entweder mit etwa 2 Mbläquivalenten eines Aoylessigsäureeetere der allgemeinen Formel II
0 R1-C- OH2 - COOR2 (II)
in der R1 und R2 die obige Bedeutung haben, so wie Ammoniak im Übereohufl oder
b) mit etwa 2 Holäquivalenten eine« S-Amino-B-alkylaorylsäureeatere der allgemeinen Forael III ■ - -
IH2 R1 - i « CH - COOR2 (III)
in der R, und R2 die obige Bedeutung haben, oder
c) mit etwa 1 Holäquivalent dee Aoyleaalgettureeetera der Formel II und etwa 1 Holäquivalent de· ß-Amino-0-alkylaoryleäureestere der forael III bei erhöhter Temperatur kondensiert«
Voreugeweiae wird das erfindungagemäe· Verfahren in einem üüeungsmittel, s.B. einem niederen aliphatischen Alkohol oder Dioxan, unter RUokfluSkoohen des Reaktionsgemisohes durchgeführt. Die Reaktionaselt beträgt vorzugsweise 1 bis 4 Stunden·
10 9 8 2 0/2203
Pas erfindungsgessäße Verfahren a), b) und c) verläuft sohematiach nach folgenden Reaktionsgleichungen
OO
-CHOf 2 R^ G-CHo-COORo-i M7-* Verbindung 1 + 2 H0O X t- c. j c.
C*
) if V CK0r2 R1-O=CH-COOR2-S* Verbindung I + H20+NH,
■■--(
CP-,
0 VRo
Il 5
CHO + R1-C-CH2-COORp + R1-C=CH-COOR Verbindung 1+2 H
Obgleich die Formel der erfindungsgemäßen 2-Trifluoraethylphenyl-dihydropyridine so gezeichnet ist? alß hätten sie die l,4-l)ihydropyridinetrukturf ist die Lage der Doppelbindungen nicht mit Sicherheit in jedem Fall bekannt<> Einige dieser Verbjndungen können die folgende 1,2-Dihydrostruktur haben:
Ό ORIGINAL
109820/2203
R2OOO" ^
Ri
Das Beispiel erläutert <iie Erfindung»
Bei^giel;
12 g dee Diäthylaoetals von o-TrifluomethyXbenasaXdehyd werden mit 50 ml 6n Salzsäure unter Stickstoff versetzt und 3 Stunden unter Rückfluß gekochtο Bas Reaktionsgemleck wird abgekühlt und die ölige von der wässrigen Schicht getrennt« Die wässrige Schicht wird mit etwa 25 ml Methylen» Chlorid gewaschen» Der Extrakt wird mit dem öl vereinigt und dazu werden 12,6 g Aoetessigsäureäthyleeter, dann 25 ml Äthanol und 5,0 ml konzentrierter wässriger Ammoniak gegeben. Die erhaltene Mischung wird 19 Stunden unter Rückfluß gekocht· dann abgekühlt und auf etwa 500 ml Eis-Wasser gegossen* Nach Filtrieren und Umkristallisieren aus Isopropyläther erhält man 3·5-Dioarbäthoxy-l,4-dihydro-216-dimethyl-4~(2-trifluormethylphenylj-pyridin vom Pp. 140 - 142,50C.
Patentansprüche
1 09820/2203

Claims (2)

  1. Patentansprüche
    .1'. lr4-»Bih.yäro-4-{2-trifluormethylphenyl}-pyr:Ldine der allgemeinen Formel X
    CP3
    B2OOC —f V- 000E2
    in der H, und Rp Alkylreste mit 1 bis 6 Kohlenetoffatomen bedauten.
  2. 2. 3 t5-Di carbäthoxy-1,4~dihydro-2,6-dimethyl-4-(2-trifluoraiethyl phenyl )-pyridin<,
    '5. Verfahren zur Herstellung von 1,4-Dihydro-4-(2-trifluormethylphenyl}~pyridinen nach Anspruch 1, dadurch gekennzeichnet, daß man etwa 1 Holäquivalent o-Trifluormethylbenzaldehyd
    a) entweder mit etwa 2 Moläquivalenten einea Aoyleseigsäureesters der allgemeinen Formel II
    0 H1 - C - OH2 - COOR2 (II) '
    in der R-, und R2 die obige Bedeutung haben sowie Ammoniak im Überschuß oder
    b) mit etwa 2 Holäquivalenten eineβ 3-Amino-ß-alkylacrylitture- eatere der allgemeinen Formel IXX
    109820/2203
    NE2
    - O * CH - COOR2 ΜΙΪ)
    in der R, und R2 die obige Ledeutung heben oder
    c) mit etwa 1 Moläquivalent des Acylsüsigsäureestera formel II und ©twa 1 Moläqu: valent des ö-Amino-Ö-alk.rlacryX· aäureesters der Formel III 1 ei erhöhter Temperatur kmdensiert.
    4» Verfahren nach Anspruch 3: dadurch gekennzeichnet, daß man die Kcndenaationsreaktion in eimern Löaungemittel unter Rückflußkothen durchführt.
    BAD
    1 09820/2203
DE1695826A 1967-02-07 1968-02-01 33-Dicarbalkoxy-l,4-dihydro-2,6-dimethyl-4-(2-trifluonnethy!phenyl)-pyridin Expired DE1695826C3 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US61439367A 1967-02-07 1967-02-07

Publications (3)

Publication Number Publication Date
DE1695826A1 true DE1695826A1 (de) 1971-05-13
DE1695826B2 DE1695826B2 (de) 1977-07-14
DE1695826C3 DE1695826C3 (de) 1978-03-23

Family

ID=24461057

Family Applications (1)

Application Number Title Priority Date Filing Date
DE1695826A Expired DE1695826C3 (de) 1967-02-07 1968-02-01 33-Dicarbalkoxy-l,4-dihydro-2,6-dimethyl-4-(2-trifluonnethy!phenyl)-pyridin

Country Status (13)

Country Link
US (1) US3441648A (de)
BE (1) BE710391A (de)
CH (1) CH498113A (de)
DE (1) DE1695826C3 (de)
DK (1) DK131819C (de)
ES (1) ES350204A1 (de)
FI (1) FI49299C (de)
FR (2) FR7046M (de)
GB (1) GB1167447A (de)
IE (1) IE31932B1 (de)
IL (1) IL29354A (de)
NL (1) NL156135B (de)
SE (1) SE337024B (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2900537A1 (de) * 1978-01-11 1979-07-12 Inst Organicheskogo Sinteza Ak 2,6-dimethyl-3,5-dimethoxykarbonyl-4- (o-difluormethoxyphenyl)-1,4-dihydropyridin
EP0239186A1 (de) * 1986-02-03 1987-09-30 The Governors of the University of Alberta Blutdrucksenkende reduzierte Pyridyl-Derivate

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1923990C3 (de) * 1969-05-10 1978-11-23 Bayer Ag Verfahren zur Herstellung von N-substituierten M-Dihydropyridin-S.S-dicarbonsäureestern
DE1963186C3 (de) * 1969-12-17 1979-02-15 Bayer Ag, 5090 Leverkusen Schwefelhaltige 1,4-Dihydropyridin-33-dicarbonsäureester
DE1963188A1 (de) * 1969-12-17 1971-06-24 Bayer Ag Neue Cyanphenyl-1,4-dihydropyridinderivate
US3862161A (en) * 1970-01-24 1975-01-21 Bayer Ag 4-pyridyl substituted 1,4-dihydropyridines
DE2005116C3 (de) * 1970-02-05 1980-02-14 Bayer Ag, 5090 Leverkusen Symmetrische 1,4-Dihydropyridin-3,5-dicarbonsäureester
GB1430961A (en) * 1972-01-22 1976-04-07 Yamanouchi Pharma Co Ltd 1-substituted-1,4-dihyddrypyridine derivatives
US3971791A (en) * 1972-03-06 1976-07-27 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3971790A (en) * 1972-03-06 1976-07-27 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3922278A (en) * 1972-06-12 1975-11-25 Sterling Drug Inc 4-(3-Nitrophenyl)-3,5-pyridinedicarboxylic acid
US4136187A (en) * 1972-08-12 1979-01-23 Bayer Aktiengesellschaft Antihypertensive 2-amino-4,5-dihydropyridine derivatives
DE2239815C2 (de) * 1972-08-12 1983-02-10 Bayer Ag, 5090 Leverkusen 2-Alkylamino-dihydropyridine, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel
SE429652B (sv) * 1978-06-30 1983-09-19 Haessle Ab 2.6-dimetyl-4-(2.3-diklorfenyl)-1.4-dihydropyridin-3.5-dikarboxylsyra-3-metylester-5-etylester
US4285955A (en) * 1978-10-31 1981-08-25 Bayer Aktiengesellschaft 1,4-Dihydropyridinecarboxylic acids
US4365063A (en) * 1981-08-31 1982-12-21 American Home Products Corporation Antihypertensive agents
US4321384A (en) * 1981-02-27 1982-03-23 American Home Products Corporation Antihypertensive agents
US4435574A (en) * 1981-07-20 1984-03-06 Kastron Valeria V 2,6-Dimethyl-3,5-dicarbomethoxy-4-(ortho-di-fluoromethylthiophenyl)-1,4-dihydropyridine
US4677101A (en) * 1983-09-26 1987-06-30 Merck & Co., Inc. Substituted dihydroazepines useful as calcium channel blockers
IE57810B1 (en) * 1984-03-27 1993-04-21 Delagrange Lab 1,4-dihydropyridine derivatives,their preparation and their use
US4652573A (en) * 1985-03-14 1987-03-24 Nelson Research & Development Co. Calcium antagonist N-hetero ester 1,4-dihydropyridines
US4849436A (en) * 1986-03-11 1989-07-18 Nelson Research & Development Co. 1,4-dihydropyridines
ATE61588T1 (de) * 1987-08-03 1991-03-15 Delagrange Lab 1,4-dihydropyridine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel.

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3221017A (en) * 1964-04-07 1965-11-30 Aldrich Chem Co Inc Aralkoxyamides of 4-phenyl-1,2,5,6-tetrahydropyridino alkanoic acids and intermediates thereof
US3325505A (en) * 1965-02-24 1967-06-13 Smith Kline French Lab 4-cycloalkyl(or cycloalkenyl)-dihydropyridines

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2900537A1 (de) * 1978-01-11 1979-07-12 Inst Organicheskogo Sinteza Ak 2,6-dimethyl-3,5-dimethoxykarbonyl-4- (o-difluormethoxyphenyl)-1,4-dihydropyridin
EP0239186A1 (de) * 1986-02-03 1987-09-30 The Governors of the University of Alberta Blutdrucksenkende reduzierte Pyridyl-Derivate

Also Published As

Publication number Publication date
NL156135B (nl) 1978-03-15
DK131819C (da) 1976-02-09
DE1695826B2 (de) 1977-07-14
ES350204A1 (es) 1969-04-16
SE337024B (de) 1971-07-26
NL6801710A (de) 1968-08-08
GB1167447A (en) 1969-10-15
DE1695826C3 (de) 1978-03-23
US3441648A (en) 1969-04-29
IE31932B1 (en) 1973-02-21
CH498113A (de) 1970-10-31
DK131819B (da) 1975-09-08
FI49299B (de) 1975-01-31
FR1574702A (de) 1969-07-18
IL29354A (en) 1971-11-29
FR7046M (de) 1969-06-16
FI49299C (fi) 1975-05-12
BE710391A (de) 1968-08-06
IE31932L (en) 1968-08-07

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