CH637390A5 - Process for the preparation of 4-oxobenzopyran compounds - Google Patents
Process for the preparation of 4-oxobenzopyran compounds Download PDFInfo
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- CH637390A5 CH637390A5 CH1218478A CH1218478A CH637390A5 CH 637390 A5 CH637390 A5 CH 637390A5 CH 1218478 A CH1218478 A CH 1218478A CH 1218478 A CH1218478 A CH 1218478A CH 637390 A5 CH637390 A5 CH 637390A5
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- ester
- rsa
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- 238000000034 method Methods 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims description 5
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical class C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 150000002148 esters Chemical class 0.000 claims abstract description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 230000003647 oxidation Effects 0.000 claims abstract description 7
- QDMPKKFNRFFSNK-UHFFFAOYSA-N n-(2h-tetrazol-5-yl)formamide Chemical group O=CNC1=NN=NN1 QDMPKKFNRFFSNK-UHFFFAOYSA-N 0.000 claims abstract description 4
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims abstract description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract description 3
- 230000015572 biosynthetic process Effects 0.000 claims abstract 2
- 238000003786 synthesis reaction Methods 0.000 claims abstract 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 150000002430 hydrocarbons Chemical group 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 229940117975 chromium trioxide Drugs 0.000 claims description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 4
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims description 4
- 239000012286 potassium permanganate Substances 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- BCEIUDAMUFAQMG-UHFFFAOYSA-M CC(C)(C)O[Cr](O)(=O)=O Chemical compound CC(C)(C)O[Cr](O)(=O)=O BCEIUDAMUFAQMG-UHFFFAOYSA-M 0.000 claims description 3
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- PXLIDIMHPNPGMH-UHFFFAOYSA-N sodium chromate Chemical compound [Na+].[Na+].[O-][Cr]([O-])(=O)=O PXLIDIMHPNPGMH-UHFFFAOYSA-N 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 238000006476 reductive cyclization reaction Methods 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 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 in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/92—Naphthopyrans; Hydrogenated naphthopyrans
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
A process is described for the synthesis of a compound of formula I <IMAGE> in which R5, R6, R7 and R8 may be various substituents, and E is a -COOH group or an N-(tetrazol-5-yl)carboxamide group, or a salt of the latter which is acceptable from the pharmaceutical viewpoint, which process includes a selective oxidation of a compound of formula II or IV: <IMAGE> or of an ester of one of them; for each pair of Y and Z, Z is a hydrogen atom and Y is either a hydrogen atom or a hydroxyl group.
Description
**ATTENTION** debut du champ DESC peut contenir fin de CLMS **.
ou d'un ester de celui-ci tel que défini à la revendication 1, dans lequel E et M sont définis comme dans la revendication 3, R,C, R6C, R7C et R8C ont la même signification que Rsa, Rsa, R7a et R8a dans la revendication 1, sauf qu'un des symboles R5C, R6C, R7c et R8C neut être un grouDe de fomule (X):
EMI2.1
ou un ester de celui-ci tel que défini ci-dessus, ou R6C et R7C forment respectivement les groupes - COCH = CHE et - OM, dans lesquels
E, X et M ont la même définition que dans la revendication 3.
L'invention a pour objet un procédé pour la préparation d'un
EMI2.2
dans lequel R5 est un atome d'hydrogène ou un groupe hydroxyle, R5 et R7 forment ensemble une chaîne -(CH2)4- ou - COCH = CHE - O - et R8 est un groupe propyle, ou alors un d'entre R R5, R7 et R8 est un groupe de formule V:
EMI2.3
dans lequel X représente une chaîne d'hydrocarbure, substituée à choix par un groupe -OH et contenant entre 2 et 10 atomes de carbone, et les groupes d'entre R5, R5, R7 et R8 qui restent sont tous des atomes d'hydrogène, E est un groupe - COOH ou un groupe N-(tétrazol-5-yl) carboxamide, ou un sel pharmaceutiquement acceptable de celui-ci.
Ledit procédé est caractérisé en ce qu'on effectue l'oxydation sélective d'un composé de formule II ou IV:
EMI2.4
ou d'un ester de ceux-ci possédant une chaîne hydrocarbonée comprenant de 1 à 10 atomes de carbone, dans lequel Rsa, R5, R7a et
R8a ont la même signification que R5, R5, R, et R8 ci-dessus, à l'exception du fait qu'un des symboles R5a, Rsa, R7a et R88 peut être un groupe de formule VI ou VIII:
:
EMI2.5
ou un ester de l'un d'eux tel que défini ci-dessus, et X est défini comme ci-dessus, ou R58 et R78 forment ensemble une chaîne -CYZCH =CE'O- ou -CH=CH-CHE-O-, ou un ester de l'un d'entre eux tel que défini ci-desus au lieu d'une chaîne - COCH = CE - O - et, pour chaque paire d'y et Z, Z est un atome d'hydrogène et Y est un atome d'hydrogène ou un groupe hydroxyle et, le cas échéant, convertit le composé ainsi obtenu en un sel pharmaceutiquement acceptable.
La réaction d'oxydation peut être effectuée par l'utilisation, par exemple, de chromate ou de bichromate de sodium, de trioxyde de chrome (par exemple sous la forme de son complexe de pyridine), de chromate de t-butyle ou, de préférence, de permanganate de potassium dans un solvant qui est inerte dans les conditions de la réaction, par exemple l'acide acétique, l'anhydride acétique, le tétrachlorure de carbone, la pyridine, I'acétone ou le benzène, ou un mélange de solvants, par exemple une solution aqueuse d'acétone ou un mélange acide acétique/anhydride acétique. La réaction peut être effectuée à une température située entre 10 et 80 C environ. Nous préférons utiliser une quantité d'oxydant juste suffisant à l'oxydation voulue.
Les composés de formule II, dans lesquels Y est un atome d'hydrogène ou un groupe hydroxyle, peuvent être synthétisés par cyclisation d'un composé de formule III:
EMI2.6
ou d'un ester de celui-ci, dans lequel E est défini comme ci-dessus, R5b, Rsb, R7b et R8b ont la même signification que R5a, R5, R78 et R88 ci-dessus, sauf que l'un d'entre R5b, Rsb, R7b et R8b peut être
EMI2.7
d'un acide minéral tel que l'acide chlorhydrique dans un solvant qui est inerte dans les conditions de la réaction, par exemple l'éthanol, à une température située entre 20 et 80 C environ. Lorsque Rx est un groupe -OH protégé, le groupe protecteur peut être enlevé après que la cyclisation a été effectuée. De tels groupes protecteurs comprennent le groupe acétyle.
Les composés de formule IV, qui ne contiennent pas de groupe de formule VI, peuvent être synthétisés par cyclisation réductrice en utilisant, par exemple, le borohydrure de sodium, suivi d'un traitement à l'acide acétique, d'un composé de formule IX:
EMI3.1
ou d'un ester de celui-ci, dans lequel E et M sont définis comme cidessus, R8c, R6C, R7c et R8C ont la même signification que Rsa, R5, R78 et R8a ci-dessus, sauf que l'un d'entre RsC, R6C, R7c et R8C peut être un groupe de formule X:
:
EMI3.2
ou un ester de celui-ci, ou alors R6C et R7c sont respectivement les groupes - COCH = CHE et - OM, dans lequel E, M et X sont définis comme ci-dessus.
Lorsque X est une chaîne d'hydrocarbure substituée par un groupe -OH, ce groupe -OH peut être protégé, si nécessaire, sous forme d'acétate ou d'éther méthylique, durant une ou plusieurs étapes du procédé, puis le protecteur est éliminé.
Dans les réactions ci-dessus, le terme un ester de celui-ci signifie un ester du groupe - COOH possédant une chaîne hydrocarbonée deCI àCl0.
Les composés de formule I et leurs dérivés acceptables du point de vue pharmaceutique et, en particulier, les sels, par exemple les sels de sodium de ceux-ci, sont efficaces dans le traitement de certaines situations, dans lesquelles les réactions antigène-anticorps sont responsables de maladies, par exemple l'asthme d'origine allergique.
Un composé spécifique de formule I qui peut être mentionné est le cromoglycate disodique.
L'invention peut être illustrée, mais non restreinte, par les exemples suivants:
Exemple 1
1,3-Bis- (2-carbéthoxy-40xo-[4H]-l -benzopyran5-yloxy) propan- 2-ol
Un mélange de I ,3-bis-(2-carbéthoxy-[4H]-I-benzopyran-5- yloxy)-propan-2-ol (1 mmol), de permanganate de potassium (5 mmol) et d'acétone (30 ml) est brassé à température ambiante jusqu'à ce que la couleur du permanganate disparaisse et que la réaction soit teminée. Le mélange réactionnel est filtré et le dioxyde de manganèse est lavé avec du chloroforme. Les filtrats rassemblés sont évaporés à sec et le solide obtenu est recristallisé dans du dioxane aqueux pour donner le composé du titre de l'exemple, P.F.
184-187"C.
Exemple 2
Diéthyl 4,6-dioxo-l0-propyl-[4H], f6Hj-benzo- (1,2-b-; 5,4-b')dipyran-2, 8-dicarboxylate
Un mélange de diéthyl 10-propyl-[2H], [8H]-benzo-(1,2-b; 5,4b')-dipyran-2,8-dicarboxylate (1 mmol), de complexe trioxyde de chrome/pyridine (10 mmol) et de dichlorméthane (30 ml) est brassé sous azote pendant 24 h. On ajoute une solution aqueuse de bisulfate de sodium à 5% (20 ml) et de l'acide sulfurique concentré (1 ml) au mélange réactionnel. Cela est extrait au chloroforme et les extraits sont rassemblés, séchés et évaporés à sec. Le résidu est recristallisé dans l'éthanol pour donner le composé du titre de l'exemple,
P.F. 169-171"C.
** ATTENTION ** start of the DESC field may contain end of CLMS **.
or an ester thereof as defined in claim 1, wherein E and M are defined as in claim 3, R, C, R6C, R7C and R8C have the same meaning as Rsa, Rsa, R7a and R8a in claim 1, except that one of the symbols R5C, R6C, R7c and R8C cannot be a group of form (X):
EMI2.1
or an ester thereof as defined above, or R6C and R7C respectively form the groups - COCH = CHE and - OM, in which
E, X and M have the same definition as in claim 3.
The subject of the invention is a process for the preparation of a
EMI2.2
in which R5 is a hydrogen atom or a hydroxyl group, R5 and R7 together form a chain - (CH2) 4- or - COCH = CHE - O - and R8 is a propyl group, or one of R R5 , R7 and R8 is a group of formula V:
EMI2.3
in which X represents a hydrocarbon chain, optionally substituted by a group -OH and containing between 2 and 10 carbon atoms, and the groups of R5, R5, R7 and R8 which remain are all hydrogen atoms , E is a group - COOH or an N- (tetrazol-5-yl) carboxamide group, or a pharmaceutically acceptable salt thereof.
Said method is characterized in that the selective oxidation of a compound of formula II or IV is carried out:
EMI2.4
or an ester thereof having a hydrocarbon chain comprising from 1 to 10 carbon atoms, in which Rsa, R5, R7a and
R8a have the same meaning as R5, R5, R, and R8 above, except that one of the symbols R5a, Rsa, R7a and R88 can be a group of formula VI or VIII:
:
EMI2.5
or an ester of one of them as defined above, and X is defined as above, or R58 and R78 together form a chain -CYZCH = CE'O- or -CH = CH-CHE-O -, or an ester of one of them as defined above instead of a chain - COCH = CE - O - and, for each pair of y and Z, Z is a hydrogen atom and Y is a hydrogen atom or a hydroxyl group and, if appropriate, converts the compound thus obtained to a pharmaceutically acceptable salt.
The oxidation reaction can be carried out by the use, for example, of sodium chromate or dichromate, chromium trioxide (for example in the form of its pyridine complex), t-butyl chromate or, preferably potassium permanganate in a solvent which is inert under the reaction conditions, for example acetic acid, acetic anhydride, carbon tetrachloride, pyridine, acetone or benzene, or a mixture of solvents, for example an aqueous acetone solution or an acetic acid / acetic anhydride mixture. The reaction can be carried out at a temperature between around 10 and 80 C. We prefer to use an amount of oxidant just sufficient for the desired oxidation.
The compounds of formula II, in which Y is a hydrogen atom or a hydroxyl group, can be synthesized by cyclization of a compound of formula III:
EMI2.6
or an ester thereof, wherein E is defined as above, R5b, Rsb, R7b and R8b have the same meaning as R5a, R5, R78 and R88 above, except that one of between R5b, Rsb, R7b and R8b can be
EMI2.7
of a mineral acid such as hydrochloric acid in a solvent which is inert under the conditions of the reaction, for example ethanol, at a temperature between about 20 and 80 C. When Rx is a protected -OH group, the protecting group can be removed after the cyclization has been carried out. Such protective groups include the acetyl group.
The compounds of formula IV, which do not contain a group of formula VI, can be synthesized by reductive cyclization using, for example, sodium borohydride, followed by treatment with acetic acid, of a compound of formula IX:
EMI3.1
or an ester thereof, in which E and M are defined as above, R8c, R6C, R7c and R8C have the same meaning as Rsa, R5, R78 and R8a above, except that one of between RsC, R6C, R7c and R8C can be a group of formula X:
:
EMI3.2
or an ester thereof, or else R6C and R7c are respectively the groups - COCH = CHE and - OM, in which E, M and X are defined as above.
When X is a hydrocarbon chain substituted by a group -OH, this group -OH can be protected, if necessary, in the form of acetate or methyl ether, during one or more stages of the process, then the protector is removed .
In the above reactions, the term an ester thereof means an ester of the group - COOH having a hydrocarbon chain from C1 to Cl0.
The compounds of formula I and their pharmaceutically acceptable derivatives and, in particular, the salts, for example the sodium salts thereof, are effective in the treatment of certain situations, in which the antigen-antibody reactions are responsible for diseases, for example allergic asthma.
A specific compound of formula I which may be mentioned is disodium cromoglycate.
The invention can be illustrated, but not limited, by the following examples:
Example 1
1,3-Bis- (2-carbethoxy-40xo- [4H] -l -benzopyran5-yloxy) propan- 2-ol
A mixture of I, 3-bis- (2-carbethoxy- [4H] -I-benzopyran-5-yloxy) -propan-2-ol (1 mmol), potassium permanganate (5 mmol) and acetone ( 30 ml) is stirred at room temperature until the color of the permanganate disappears and the reaction is finished. The reaction mixture is filtered and the manganese dioxide is washed with chloroform. The combined filtrates are evaporated to dryness and the solid obtained is recrystallized from aqueous dioxane to give the title compound of the example, P.F.
184-187 "C.
Example 2
Diethyl 4,6-dioxo-10-propyl- [4H], f6Hj-benzo- (1,2-b-; 5,4-b ') dipyran-2, 8-dicarboxylate
A mixture of diethyl 10-propyl- [2H], [8H] -benzo- (1,2-b; 5,4b ') - dipyran-2,8-dicarboxylate (1 mmol), of chromium trioxide / pyridine complex (10 mmol) and dichlormethane (30 ml) is stirred under nitrogen for 24 h. A 5% aqueous sodium bisulfate solution (20 ml) and concentrated sulfuric acid (1 ml) are added to the reaction mixture. This is extracted with chloroform and the extracts are combined, dried and evaporated to dryness. The residue is recrystallized from ethanol to give the title compound of the example,
Mp 169-171 "C.
Claims (4)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4952777 | 1977-11-29 | ||
| GB4952577 | 1977-11-29 | ||
| GB7832082 | 1978-08-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH637390A5 true CH637390A5 (en) | 1983-07-29 |
Family
ID=27260092
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1218478A CH637390A5 (en) | 1977-11-29 | 1978-11-28 | Process for the preparation of 4-oxobenzopyran compounds |
| CH143383A CH639968A5 (en) | 1977-11-29 | 1983-03-15 | Process for the preparation of 4-oxobenzopyran compounds |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH143383A CH639968A5 (en) | 1977-11-29 | 1983-03-15 | Process for the preparation of 4-oxobenzopyran compounds |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS5498769A (en) |
| CA (1) | CA1117540A (en) |
| CH (2) | CH637390A5 (en) |
| DK (1) | DK528378A (en) |
| FI (1) | FI783616A (en) |
| PT (1) | PT68839A (en) |
| SE (2) | SE7812089L (en) |
-
1978
- 1978-11-23 SE SE7812089A patent/SE7812089L/en unknown
- 1978-11-27 CA CA000316937A patent/CA1117540A/en not_active Expired
- 1978-11-27 FI FI783616A patent/FI783616A/en unknown
- 1978-11-27 DK DK528378A patent/DK528378A/en not_active Application Discontinuation
- 1978-11-28 CH CH1218478A patent/CH637390A5/en not_active IP Right Cessation
- 1978-11-28 PT PT68839A patent/PT68839A/en unknown
- 1978-11-29 JP JP14669478A patent/JPS5498769A/en active Pending
-
1983
- 1983-03-15 CH CH143383A patent/CH639968A5/en not_active IP Right Cessation
- 1983-09-16 SE SE8304996A patent/SE8304996D0/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| FI783616A (en) | 1979-05-30 |
| JPS5498769A (en) | 1979-08-03 |
| PT68839A (en) | 1978-12-01 |
| SE8304996L (en) | 1983-09-16 |
| SE8304996D0 (en) | 1983-09-16 |
| DK528378A (en) | 1979-05-30 |
| CA1117540A (en) | 1982-02-02 |
| CH639968A5 (en) | 1983-12-15 |
| SE7812089L (en) | 1979-05-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |