NO140595B - PROCEDURE FOR THE PREPARATION OF 1,8-NAFTYRIDINE DERIVATIVES - Google Patents
PROCEDURE FOR THE PREPARATION OF 1,8-NAFTYRIDINE DERIVATIVES Download PDFInfo
- Publication number
- NO140595B NO140595B NO744718A NO744718A NO140595B NO 140595 B NO140595 B NO 140595B NO 744718 A NO744718 A NO 744718A NO 744718 A NO744718 A NO 744718A NO 140595 B NO140595 B NO 140595B
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- Prior art keywords
- methyl
- naphthyridine
- dihydro
- oxo
- ethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- 239000011630 iodine Substances 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- -1 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(cyclohexyl-methyl-pyridinium)-iodide Chemical compound 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 150000005058 1,8-naphthyridines Chemical class 0.000 description 1
- KFDHIILYKICEGY-UHFFFAOYSA-M 1-ethyl-7-methyl-3-(1-methyl-2-phenylpyridin-1-ium-3-carbonyl)-1,8-naphthyridin-4-one iodide Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C=1C(=[N+](C=CC1)C)C1=CC=CC=C1 KFDHIILYKICEGY-UHFFFAOYSA-M 0.000 description 1
- ZPVXFTFVNMMWJX-UHFFFAOYSA-N 1-ethyl-7-methyl-3-(3-phenylpropanoyl)-1,8-naphthyridin-4-one Chemical compound C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(CCC1=CC=CC=C1)=O ZPVXFTFVNMMWJX-UHFFFAOYSA-N 0.000 description 1
- FQDNITWZGPQXBT-UHFFFAOYSA-N 1-ethyl-7-methyl-3-pentanoyl-1,8-naphthyridin-4-one Chemical compound C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(CCCC)=O FQDNITWZGPQXBT-UHFFFAOYSA-N 0.000 description 1
- CYDFIAGFVIGXQJ-UHFFFAOYSA-N 1-ethyl-7-methyl-3-propanoyl-1,8-naphthyridin-4-one Chemical compound CC1=CC=C2C(=O)C(C(=O)CC)=CN(CC)C2=N1 CYDFIAGFVIGXQJ-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- ICZPXVNCDPEYSR-UHFFFAOYSA-N 3-butanoyl-1-ethyl-7-methyl-1,8-naphthyridin-4-one Chemical compound C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(CCC)=O ICZPXVNCDPEYSR-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QUXLCYFNVNNRBE-UHFFFAOYSA-N 6-methylpyridin-2-amine Chemical compound CC1=CC=CC(N)=N1 QUXLCYFNVNNRBE-UHFFFAOYSA-N 0.000 description 1
- XZOVCSPCZQGKJD-UHFFFAOYSA-N C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(CCC1CCCCC1)=O Chemical compound C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(CCC1CCCCC1)=O XZOVCSPCZQGKJD-UHFFFAOYSA-N 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- OTBBVGDVKUGFQK-UHFFFAOYSA-M [Br-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C1=C(C(=[N+](C=C1)C)C)C Chemical compound [Br-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C1=C(C(=[N+](C=C1)C)C)C OTBBVGDVKUGFQK-UHFFFAOYSA-M 0.000 description 1
- ZZDGZJIFEMSRFR-UHFFFAOYSA-M [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C1=C(C(=[N+](C=C1)C)C)C Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C1=C(C(=[N+](C=C1)C)C)C ZZDGZJIFEMSRFR-UHFFFAOYSA-M 0.000 description 1
- NXOWTBYJIBWPAB-UHFFFAOYSA-M [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C=1[N+](=C(C2=CC=CC=C2C1)C)CC Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C=1[N+](=C(C2=CC=CC=C2C1)C)CC NXOWTBYJIBWPAB-UHFFFAOYSA-M 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 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
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Description
Foreliggende oppfinnelse vedrorer fremstilling av 1-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyre og andre l-alkyl-7-metyl-4-okso-1,4-dihydro-l,8-naftyridin-3-karboksylsyrer. l-alkyl-7-metyl-4-okso-l, 4-r.dihydro-l, 8-naftyridin-3-karboksyl-syrer er velkjente verdifulle antibakterielle midler som anvendes innen terapien. Disse forbindelser ble fremstilt ved alkylering med etterfolgende hydrolyse av 7-metyl-4-okso-3-alkoksykarbony1-1,4-dihydro-l,8-naftyridin (britisk patent nr. l.ooo.892). Det er i henhold til foreliggende oppfinnelse funnet at l-alkyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksyl-syrer av den generelle formel (I) hvor alkyl betegner alkyl med 1-6 C-atomer kan fremstilles i ren tilstand med godt utbytte ved å underkaste forbindelser av den generelle formel (II) The present invention relates to the preparation of 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and other 1-alkyl-7-methyl-4-oxo-1,4- dihydro-1,8-naphthyridine-3-carboxylic acids. 1-Alkyl-7-methyl-4-oxo-1,4-r.dihydro-1,8-naphthyridine-3-carboxylic acids are well-known valuable antibacterial agents used in therapy. These compounds were prepared by the alkylation with subsequent hydrolysis of 7-methyl-4-oxo-3-alkoxycarbonyl-1,4-dihydro-1,8-naphthyridine (British Patent No. 1,000,892). According to the present invention, it has been found that 1-alkyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acids of the general formula (I) where alkyl denotes alkyl with 1-6 C atoms can be prepared in the pure state in good yield by subjecting compounds of the general formula (II)
hvori R<1> betyr hydrogen eller en alkylgruppe med 1-6 karbonatomer wherein R<1> means hydrogen or an alkyl group with 1-6 carbon atoms
R<2> betyr -(CH2)m-CH3, -(CH2)n~fenyl eller -(CH2)r cykloalkyl, R<2> means -(CH2)m-CH3, -(CH2)n~phenyl or -(CH2)r cycloalkyl,
Y betyr pyridino, pikolino, kinolino eller isokinolino, Y means pyridino, picolino, quinolino or isoquinolino,
Z er et halogenid-, sulfat-, fosfat-, perklorat- eller nitratanion, n, m og p er heltall fra 0-5, alkyl har ovenfor nevnte betydning, og cykloalkyl har 3-6 C-atomer, Z is a halide, sulfate, phosphate, perchlorate or nitrate anion, n, m and p are integers from 0-5, alkyl has the meaning mentioned above, and cycloalkyl has 3-6 C atoms,
hydrolyse i nærvær av et alkalimetallhydroksyd. hydrolysis in the presence of an alkali metal hydroxide.
Denne fremgangsmåte er fordelaktig ved at det anvendes utgangsmaterialer som lett kan renses. This method is advantageous in that starting materials are used that can be easily cleaned.
I henhold til en foretrukket utforelsesform av foreliggende oppfinnelse, behandles en forbindelse av den generelle formel (II) med en vandig alkoholisk,fortrinnsvis etanolisk natriumhydroksyd eller kaliumhydroksydopplosning. Hydrolysen kan utfores ved en temperatur i området 2o - 15o°C, fortrinnsvis 8o - 12o°C. According to a preferred embodiment of the present invention, a compound of the general formula (II) is treated with an aqueous alcoholic, preferably ethanolic sodium hydroxide or potassium hydroxide solution. The hydrolysis can be carried out at a temperature in the range 2o - 15o°C, preferably 8o - 12o°C.
Forbindelsen av formel (I) kan presipiteres ved å surgjore The compound of formula (I) can be precipitated by acidification
i rekajsonsblandingen, fortrinnsvis ved tilsetning av en syre. Mineralsyre såsom saltsyre eller organiske syrer, såsom eddiksyre eller maursyre kan anvendes for dette formål. in the shrimp mixture, preferably by adding an acid. Mineral acid such as hydrochloric acid or organic acids such as acetic acid or formic acid can be used for this purpose.
Utgangsmaterialer av den generelle formel (II) er nye forbindelser og kan fremstilles på folgende måte: 2-amino-6-metyl-pyridin eller et syreaddisjonssalt derav konden-seres med en forbindelse av den generelle formel (III) Starting materials of the general formula (II) are new compounds and can be prepared in the following way: 2-amino-6-methyl-pyridine or an acid addition salt thereof is condensed with a compound of the general formula (III)
De således erholdte forbindelser av formel (IV) underkastes deretter en ringslutning, hvoretter de derved erholdte 1, 8 naftyridin-derivater av formel (V) The thus obtained compounds of formula (IV) are then subjected to a ring closure, after which the thereby obtained 1,8 naphthyridine derivatives of formula (V)
N-alkyleres. De således erholdte forbindelser av formel (VI) omsettes med en heterocyklisk base inneholdende et tertiært nitrogenatom eller med trialkylamin i nærvær av et halogen til å gi utgangsforbindelsene ifolge formel (II). N-alkylated. The thus obtained compounds of formula (VI) are reacted with a heterocyclic base containing a tertiary nitrogen atom or with trialkylamine in the presence of a halogen to give the starting compounds according to formula (II).
Anionet kan utbyttes med et annet anion. The anion can be exchanged with another anion.
Oppfinnelsen illustreres i de folgende eksempler. The invention is illustrated in the following examples.
EKSEMPEL 1 EXAMPLE 1
En blanding av 1,22 g l-etyl-7-metyl-3-propionyl-4-okso-l,4-dihydro-1,8-naftyridin, lo ml pyridin og 1,27 g jod blir omrort ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Den således erholdte l-etyl-7-metyl-4-oksp-l,4-dihydro-1,8-naftyridin-3-karbonyl-(metyl-metyl-pyridinium)jodid blir blandet med 25 ml av en lo%'ig natriumhydroksydopplosning og oppvarmet til koking. Den herved dannede klare opplosning blir avkjolt, ekstrahert med kloroform, klaret med dctivert trekull og filtrert fra. Filtratet blir surgjort med saltsyre. A mixture of 1.22 g of 1-ethyl-7-methyl-3-propionyl-4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of pyridine and 1.27 g of iodine is stirred at 10°C , after which the reaction mixture is evaporated in vacuo. The 1-ethyl-7-methyl-4-oxp-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(methyl-methyl-pyridinium) iodide thus obtained is mixed with 25 ml of a sodium hydroxide solution and heated to boiling. The clear solution thus formed is cooled, extracted with chloroform, clarified with activated charcoal and filtered off. The filtrate is acidified with hydrochloric acid.
De presipiterte krystaller blir frafiltrert og vasket med vann. Smeltepunktet til l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyren er 224-226°C. Utbytte 93%. The precipitated crystals are filtered off and washed with water. The melting point of the 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid is 224-226°C. Yield 93%.
EKSEMPEL 2 EXAMPLE 2
En blanding av 1,29 g l-etyl-7-metyl-3-butyryl-4-okso-l,4-dihydro-1,8-naftyridin, lo ml isokinolin og 1,27 g jod blir omrort ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Den således erholdte l-etyl-7-metyl-4-okso-1,4-dihydro-l,8-naftyridin-3-karbonyl-(etyl-metyl-isokinolinium)-jodid blir blandet med 25 ml av en 10%'s natriumhydroksydoppløs-ning og oppvarmet til koking. Den herved dannede klare oppløs-ning blir avkjølt, ekstrahert med kloroform, klaret med aktivert trekull og filtrert fra. Filtratet blir surgjort med saltsyre. A mixture of 1.29 g of 1-ethyl-7-methyl-3-butyryl-4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of isoquinoline and 1.27 g of iodine is stirred at 10°C , after which the reaction mixture is evaporated in vacuo. The 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(ethyl-methyl-isoquinolinium)-iodide thus obtained is mixed with 25 ml of a 10% s sodium hydroxide solution and heated to boiling. The clear solution thus formed is cooled, extracted with chloroform, clarified with activated charcoal and filtered off. The filtrate is acidified with hydrochloric acid.
De presipiterte krystaller blir frafiltrert og vasket med vann. Smeltepunktet til l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyre er 225-227°C. The precipitated crystals are filtered off and washed with water. The melting point of 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid is 225-227°C.
EKSEMPEL 3 EXAMPLE 3
En blanding av 1,36 g l-etyl-7-metyl-3-valeroyl-4-okso-l,4-dihydro-1,8-naftyridin, 10 ml picolin og 1,27 g jod blir omrort ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Den således erholdte l-etyl-7-metyl-4-okso-l,4-dihydro-1,8-naftyridin-3-karbonyl-(propyl-metyl-p£colinium)- A mixture of 1.36 g of 1-ethyl-7-methyl-3-valeroyl-4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of picoline and 1.27 g of iodine is stirred at 10°C , after which the reaction mixture is evaporated in vacuo. The thus obtained 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(propyl-methyl-p£colinium)-
jodid blir blandet med 25 ml av en lo%'ig natriumhydroksydopplosning og oppvarmet til koking. Den dannede klare opp-løsning blir avkjolt, ekstrahert med kloroform, klaret med aktivert trekull og filtrert fra. Filtratet blir surgjort med saltsyre. De presipiterte krystaller blir filtrert fra og vasket med vann. Smeltepunktet til l-etyl-7-metyl-4-okso-1,4-dihydro-l,8-naftyridin-3-karboksylsyre er 223-225°C. iodide is mixed with 25 ml of a 1% sodium hydroxide solution and heated to boiling. The clear solution formed is cooled, extracted with chloroform, clarified with activated charcoal and filtered off. The filtrate is acidified with hydrochloric acid. The precipitated crystals are filtered off and washed with water. The melting point of 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid is 223-225°C.
EKSEMPEL 4 EXAMPLE 4
En blanding av 1,53 g l-etyl-7-metyl-3-fenacetyl-4-okso-l,4-dihydro-1,8-naftyridin, lo ml pyridin og 1,27 g jod blir om- A mixture of 1.53 g of 1-ethyl-7-methyl-3-phenacetyl-4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of pyridine and 1.27 g of iodine is re-
rort ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Det således erholdte l-etyl-7-metyl-4-okso-l,4-dihydro-1,8-naftyridin-3-karbonyl-(fenyl-metyl-pyridinium)-jodid blir blandet med 25 ml av lo%'ig natriumhydroksydopplosning og oppvarmet til koking. Den herved dannede klare opplosning blir avkjolt, ekstrahert med kloroform, klaret med aktivert trekull og filtrert fra. Filtratet blir surgjort med saltsyre. stirred at 10°C, after which the reaction mixture is evaporated in vacuo. The 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(phenyl-methyl-pyridinium)-iodide thus obtained is mixed with 25 ml of sodium hydroxide solution and heated to boiling. The clear solution thus formed is cooled, extracted with chloroform, clarified with activated charcoal and filtered off. The filtrate is acidified with hydrochloric acid.
De presipiterte krystallene blir frafiltrert og vasket med The precipitated crystals are filtered off and washed with
vann. Smelte-punktet til l-etyl-7-metyl-4-okso-l,4-dihydro-1,8-naftyridin-3-karboksylsyre er 224-226°C. water. The melting point of 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid is 224-226°C.
EKSEMPEL 5 EXAMPLE 5
En blanding av l,6o g l-etyl-7-metyl-3-(3-fenyl-propionyl)-4-okso-l,4-dihydro-l,8-naftyridin, lo ml kinolin og 1,27 g jod blir omrort ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Det således erholdte l-etyl-7-metyl-4-okso-1,4-dihydro-3-karbonyl-(benzyl-metyl-kinolinium)-iodid blir blandet med 25 ml av en lo%'ig natriumhydroksydopplosning A mixture of 1.60 g of 1-ethyl-7-methyl-3-(3-phenyl-propionyl)-4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of quinoline and 1.27 g of iodine is stirred at 10°C, after which the reaction mixture is evaporated in vacuo. The thus obtained 1-ethyl-7-methyl-4-oxo-1,4-dihydro-3-carbonyl-(benzyl-methyl-quinolinium)-iodide is mixed with 25 ml of a 10% sodium hydroxide solution
i og oppvarmet til koking. Den derved dannede klare opplosning in and heated to boiling. It thereby formed a clear solution
blir avkjolt, ekstrahert med kloroform, klaret med aktivert trekull og filtrert fra. Filtratet blir surgjort med saltsyre. is cooled, extracted with chloroform, clarified with activated charcoal and filtered off. The filtrate is acidified with hydrochloric acid.
De presipiterte krystaller blir frafiltrert og vasket med The precipitated crystals are filtered off and washed with
vann. Smeltepunktet til l-etyl-7-metyl-4-okso-l,4-dihydro-1,8-naftyridin-3-karboksylsyre er 227-228°C. water. The melting point of 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid is 227-228°C.
EKSEMPEL 6 EXAMPLE 6
En blanding av 1,56 g l-etyl-7-metyl-3-cykloheksyl-acetyl-4-okso-1, 4-idihydro-1, 8-naftyridin, lo ml pyridin og 1,27 g jod blir omrort ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Det således erholdte l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-(cykloheksyl-metyl-pyridinium)-jodid blir blandet med 25 ml av en lo%'ig natriumhydroksydopplosning og oppvarmet til koking. Den derved dannede klare opplosning blir avkjolt, ekstrahert med kloroform, klaret med aktivert trekull og frafiltrert. A mixture of 1.56 g of 1-ethyl-7-methyl-3-cyclohexyl-acetyl-4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of pyridine and 1.27 g of iodine is stirred at °C, after which the reaction mixture is evaporated in vacuo. The 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(cyclohexyl-methyl-pyridinium)-iodide thus obtained is mixed with 25 ml of a 10% ig sodium hydroxide solution and heated to boiling. The resulting clear solution is cooled, extracted with chloroform, clarified with activated charcoal and filtered off.
Filtratet blir surgjort med saltsyre. De presipiterte krystaller blir frafiltrert og vasket med vann. Smeltepunktet til 1-etyl-7-metyl-4-okso-l,4> dihydro-1,8-naftyridin-3-karboksylsyre er 226-228°C. The filtrate is acidified with hydrochloric acid. The precipitated crystals are filtered off and washed with water. The melting point of 1-ethyl-7-methyl-4-oxo-1,4>dihydro-1,8-naphthyridine-3-carboxylic acid is 226-228°C.
EKSEMPEL 7 EXAMPLE 7
En blanding av 1,63 g l-etyl-7-metyl-3-(3-cykloheksyl-propionyl)-4-okso-l,4-dihydro-l,8-naftyridin, lo ml pyridin og 1,27 g jod blir omrort ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Den således erholdte l-etyl-7-metyl-4-okso-1,4-dihydro-l,8-naftyridin-3-karbonyl-/T cykloheksyl-metyl)-metyl-pyridinium7-jodid blir blandet med 25 ml av en lo%'ig natriumhydroksydopplosning og oppvarmet til koking. A mixture of 1.63 g of 1-ethyl-7-methyl-3-(3-cyclohexyl-propionyl)-4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of pyridine and 1.27 g of iodine is stirred at 10°C, after which the reaction mixture is evaporated in vacuo. The thus obtained 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(T cyclohexyl-methyl)-methyl-pyridinium 7-iodide is mixed with 25 ml of a lo%'ig sodium hydroxide solution and heated to boiling.
Den herved dannede opplosning blir avkjolt, ekstrahert med kloroform, klaret med aktivert trekull og frafiltrert. Filtratet blir surgjort med saltsyre. De presispiterte krystallene blir filtrert fra og vasket med vann. Smeltepunktet til l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyre er 221-223°C. The resulting solution is cooled, extracted with chloroform, clarified with activated charcoal and filtered off. The filtrate is acidified with hydrochloric acid. The precipitated crystals are filtered off and washed with water. The melting point of 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid is 221-223°C.
EKSEMPEL 8 EXAMPLE 8
En blanding av 1,29 g l-etyl-7-metyl-3-(2-metyl-propionyl)-4-okso-dihydro-l,8-naftyridin, lo ml pyridin og 1,27 jod om-rores ved loo°C, hvoretter reaksjonsblandingen blir inndampet i vakuum. Den således erholde 1-ety1-7-metyl-4-okso-l, 4-dihydro-1,8-naftyridin-3-karbonyl-(dimetyl-metyl-pyridinium)-jodid blir blandet med 25 ml av en lo%'ig natriumhydroksydopplosning og oppvarmet til koking, deretter blir det avkjolt, ekstrahert med klorofform, klaret med aktivert trekull og filtrert fra. Filtratet blir surgjort med saltsyre. De presipiterte krystallene blir frafiltrert og vasket med vann. Smeltepunktet til 1-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyre er 226-228 pC. A mixture of 1.29 g of 1-ethyl-7-methyl-3-(2-methyl-propionyl)-4-oxo-dihydro-1,8-naphthyridine, 10 ml of pyridine and 1.27 of iodine is stirred at loo °C, after which the reaction mixture is evaporated in vacuo. The thus obtained 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(dimethyl-methyl-pyridinium)-iodide is mixed with 25 ml of a 10% ig sodium hydroxide solution and heated to boiling, then it is cooled, extracted with chloroform, clarified with activated charcoal and filtered off. The filtrate is acidified with hydrochloric acid. The precipitated crystals are filtered off and washed with water. The melting point of 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid is 226-228 pC.
EKSEMPEL 9 EXAMPLE 9
En blanding av 1,69 g l-etyl-7-metyl-3-(2-brom-2-metyl-propionyl-) -4-okso-l,4-dihydro-l,8-naftyridin og 5o ml pyridin blir oppvarmet til koking, hvoretter reaksjonsblandingen blir inndampet i vakuum l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-(dimetyl-metyl-pyridinium)-bromid blir blandet med 25 ml av en lo%'ig opplosning natriumhydroksyd, hvoretter blandingen blir oppvarmet til koking. Den restlige opplosning blir avkjolt, ekstrahert med kloroform, ekstraktet blir klaret og surgjort med fortynnet saltsyre. Den presipiterte 1-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyre smelter ved 225-226°C. A mixture of 1.69 g of 1-ethyl-7-methyl-3-(2-bromo-2-methyl-propionyl-)-4-oxo-1,4-dihydro-1,8-naphthyridine and 50 ml of pyridine is heated to boiling, after which the reaction mixture is evaporated in vacuo 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(dimethyl-methyl-pyridinium)-bromide is mixed with 25 ml of an aqueous solution of sodium hydroxide, after which the mixture is heated to boiling. The remaining solution is cooled, extracted with chloroform, the extract is clarified and acidified with dilute hydrochloric acid. The precipitated 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid melts at 225-226°C.
EKSEMPEL 10 EXAMPLE 10
En blanding av 2,11 g 7-mety1-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-(metyl-metyl-pyridinium)-jod, 4,55 g trietylfosfat, o,7 g kaliumkarbonat blir oppvarmet til koking. Reaksjonsblandingen blir avkjolt, heilt i en lo%'ig natriumhydroksydopplosning og den vandige reaksjonblandingen blir oppvarmet til koking. Oppløsningen blir avkjolt, ekstrahert med aktivert trekull A mixture of 2.11 g of 7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(methyl-methyl-pyridinium)-iodo, 4.55 g of triethyl phosphate, o.7 g of potassium carbonate is heated to boiling. The reaction mixture is cooled, completely in an aqueous sodium hydroxide solution and the aqueous reaction mixture is heated to boiling. The solution is cooled, extracted with activated charcoal
og frafiltrert. Filtratet blir surgjort med 2o% and filtered out. The filtrate is acidified with 2o%
saltsyre. De presipiterte krystaller blir frafiltrert, vasket med vann og torket. l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyren smelter ved 225-227°C. hydrochloric acid. The precipitated crystals are filtered off, washed with water and dried. The 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid melts at 225-227°C.
I eksemplene 2-10 var utbyttene 40 - 60%. In examples 2-10, the yields were 40 - 60%.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU73CI00001430A HU171561B (en) | 1973-12-29 | 1973-12-29 | Process for producing 1,8-naphtiridine derivatives |
| JP49007185A JPS514197A (en) | 1973-12-29 | 1974-01-16 | 1** nafuchirijinjudotaino seizoho |
| HU74CI00001522A HU171869B (en) | 1974-01-17 | 1974-12-05 | New process for preparing derivatives of 1,8-naphthyridine |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO744718L NO744718L (en) | 1975-07-28 |
| NO140595B true NO140595B (en) | 1979-06-25 |
| NO140595C NO140595C (en) | 1979-10-03 |
Family
ID=27270158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO744718A NO140595C (en) | 1973-12-29 | 1974-12-27 | PROCEDURE FOR THE PREPARATION OF 1,8-NAFTYRIDINE DERIVATIVES |
Country Status (12)
| Country | Link |
|---|---|
| AR (1) | AR207855A1 (en) |
| BG (1) | BG25986A3 (en) |
| CA (1) | CA1039285A (en) |
| CH (1) | CH613968A5 (en) |
| DD (1) | DD116034A5 (en) |
| DK (1) | DK677274A (en) |
| FI (1) | FI375874A (en) |
| GB (1) | GB1493949A (en) |
| NL (1) | NL7416925A (en) |
| NO (1) | NO140595C (en) |
| SE (1) | SE419863B (en) |
| SU (1) | SU580838A3 (en) |
-
1974
- 1974-01-01 AR AR257147A patent/AR207855A1/en active
- 1974-12-23 DK DK677274A patent/DK677274A/da not_active Application Discontinuation
- 1974-12-24 GB GB55876/74A patent/GB1493949A/en not_active Expired
- 1974-12-24 CH CH1730774A patent/CH613968A5/en not_active IP Right Cessation
- 1974-12-27 NO NO744718A patent/NO140595C/en unknown
- 1974-12-27 CA CA217,002A patent/CA1039285A/en not_active Expired
- 1974-12-27 SU SU7402092458A patent/SU580838A3/en active
- 1974-12-27 NL NL7416925A patent/NL7416925A/en not_active Application Discontinuation
- 1974-12-27 FI FI3758/74A patent/FI375874A/fi unknown
- 1974-12-27 SE SE7416323A patent/SE419863B/en unknown
- 1974-12-30 BG BG7428617A patent/BG25986A3/xx unknown
- 1974-12-30 DD DD183434A patent/DD116034A5/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DD116034A5 (en) | 1975-11-05 |
| BG25986A3 (en) | 1979-01-12 |
| NO744718L (en) | 1975-07-28 |
| NO140595C (en) | 1979-10-03 |
| SU580838A3 (en) | 1977-11-15 |
| CH613968A5 (en) | 1979-10-31 |
| DK677274A (en) | 1975-09-01 |
| CA1039285A (en) | 1978-09-26 |
| SE419863B (en) | 1981-08-31 |
| SE7416323L (en) | 1975-06-30 |
| FI375874A (en) | 1975-06-30 |
| NL7416925A (en) | 1975-07-01 |
| AR207855A1 (en) | 1976-11-08 |
| GB1493949A (en) | 1977-11-30 |
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