NO140498B - Fremgangsmaate ved fremstilling av 1,8-naftyridin-derivater - Google Patents
Fremgangsmaate ved fremstilling av 1,8-naftyridin-derivater Download PDFInfo
- Publication number
- NO140498B NO140498B NO744717A NO744717A NO140498B NO 140498 B NO140498 B NO 140498B NO 744717 A NO744717 A NO 744717A NO 744717 A NO744717 A NO 744717A NO 140498 B NO140498 B NO 140498B
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- naphthyridine
- dihydro
- oxo
- ethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- -1 picolinyl Chemical group 0.000 claims description 5
- 125000005270 trialkylamine group Chemical group 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 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 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- XHGXTOCJRSLUHE-UHFFFAOYSA-M [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C1=[N+](C=CC=C1)C Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C1=[N+](C=CC=C1)C XHGXTOCJRSLUHE-UHFFFAOYSA-M 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 150000005058 1,8-naphthyridines Chemical class 0.000 description 1
- ZEBCDVDPXRPLDP-UHFFFAOYSA-M 1-ethyl-7-methyl-3-(2-pyridin-1-ium-1-ylacetyl)-1,8-naphthyridin-4-one iodide Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C[N+]1=CC=CC=C1 ZEBCDVDPXRPLDP-UHFFFAOYSA-M 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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- MKCSZCVXAHYHQX-UHFFFAOYSA-M [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C=1C(=[N+](C=CC1)C)C Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C=1C(=[N+](C=CC1)C)C MKCSZCVXAHYHQX-UHFFFAOYSA-M 0.000 description 1
- ORKYRVMXBZDWIA-UHFFFAOYSA-N [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)CC1=[NH+]C=CC2=CC=CC=C12 Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)CC1=[NH+]C=CC2=CC=CC=C12 ORKYRVMXBZDWIA-UHFFFAOYSA-N 0.000 description 1
- XFNNRAPTEMICAG-UHFFFAOYSA-M [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C[N+]1=CC=CC2=CC=CC=C12 Chemical compound [I-].C(C)N1C=C(C(C2=CC=C(N=C12)C)=O)C(=O)C[N+]1=CC=CC2=CC=CC=C12 XFNNRAPTEMICAG-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
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000001816 cooling Methods 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
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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 l-etyl-7-metyl-4-okso-1,4-dihydro-l,8-naftyridin-3-karboksylsyre og andre l-alkyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyrer. l-alkyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksyl-syrer er velkjente verdifulle antibakterille midler, som anvendes innen terapien. Disse forbindelser ble fremstilt ved alkylering med etterfølgende hydrolyse av 7-metyl-4-okso-3-alkoksykarbonyl-l,4-dihydro-l,8-nftyridin (britisk patent nr. l.ooo.892). I henhold til foreliggende oppfinnelse er det 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 karbonatomer,
kan fremstilles i ren tilstand med godt utbytte ved å underkaste forbindelser av den generelle formel (II)
hvor Y er en pyridinyl-, picolinyl-, quinolyl- eller isoquinolylgruppe, X er et halogenid-anion, og alkyl har oven-
for nevnte betydning,
for hydrolyse.
Denne fremgangsmåte er fordelaktig ved at utgangsmaterialene lett
kan renses.
Hydrolysen utføres i nærvær av alkalimetallhydroksyder eller ut-føres i et vandig medium i nærvær av trialkylamin. For dette for-
mål kan anvendes lavere trialkylaminer såsom trimetylamin eller mere fordelaktig, trietylamin.
I henhold til en foretrukket utførelsesform av foreliggende oppfinnelse behandles en forbindelse av den generelle formel (II)
med en vandig alkoholisk, fortrinnsvis etanolisk natriumhydroksyd-eller kaliumhydroksydoppløsning. Hydrolysen kan utføres ved en temperatur i området 20 - 150°C, fortrinnsvis 80 - 120°C.
Forbindelsene av formel (I) kan presipiteres ved å surgjøre reaksjonsblandingen, fortrinnsvis ved tilsetning av en syre. Mineral-syre såsom saltsyre eller organiske syrer, såsom eddiksyre, maur-syre, etc. kan anvendes for dette formål.
En kan også gå frem ved å underkaste forbindelsen av formel (II) hydrolyse uten isolering av reaksjonsblandingen som derved erholdes.
Sam utgangsmateriale av formel (II) anvendes fortrinnsvis l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-metylpyridinium-jodid, l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-metyl-(X-picolinium)-jodid eller l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-metyl-guinoliniumjodid.
Andre 1-lavere-alkyl-derivater, såsom 1-metyl-,1-propyl- etc, kan også anvendes.
Utgangsmaterialene av den generelle formel (II) er nye forbindelser og kan fremstilles på følgende måte: 2-amino-6-metyl-pyridin eller et syreaddisjonssalt derav konden-seres med en forbindelse av formel (II) Forbindelsene av formel (IV) som derved erholdes underkastes ringslutning, hvoretter de derved erholdte 1,8-naftyridin-derivater av formelen (V) N-alkyleres. De derved erholdte forbindelser av formel (VI)
omsettes med en heterocyklisk base inneholdende et tertiært nitrogen eller med trialkylamin i nærvær av et halogen til å gi utgangsmaterialene av formel (II) . Anionet kan utbyttes med et annet anion.
Oppfinnelsen illustreres i de folgende eksempler.
EKSEMPEL 1
1 g l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-metyl-pyridinium-jodid kokes under tilbakelop i 25 ml av en 4%'ig vandig natriumhydroksydopplosning. Den erholdte opplosning surgjores med 2o%'ig saltsyre. Den presipiterte l-etyl-7-metyl-4oioksy-l, 4-dihydro-l, 8-nafiyridin-3-karboksylsyre filtreres fra. Utbytte o,5 g (97,5%). Smp. 226-227°C.
EKSEMPEL 2
Fremgangsmåten i henhold til eksempel 1 gjentas med den unn-tagelse at hydrolysen utfores i en blanding av 25 ml etanol og 25 ml av en 4%'ig natriumhydroksydopplosning. o,5 g l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksyl-syre erholdes. Utbytte 97,5%, smp. 227-228°C.
Den således erholdte l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karboksylsyre utviser ingen smeltepunktsned-settelse ved en blandet smeltepunktsbestemmelse for en autentisk prove av den nevnte forbindelse.
EKSEMPEL 3
4,4 g l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonylmetyl-pyridinium-jodid, 5o ml vann og 2,8 ml trietylamin kokes forsiktig under tilbakelop. Etter avkjoling filtreres det presipiterte produkt fra. Den således erholdte 1-etyl-7-metyl-4-okso-l,4 -dihydro-1,8-naftyridin-3-karboksylsyre smelter ved 224-225°C , utbytte 95 %.
EKSEMPEL 4
lg l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbonyl-metyl-a-picolinium-jodid kokes under tilbakelop i 25 ml 4%'ig vandig natriumhydroksydopplosning. Blandingen surgjores med saltsyre og den presipiterte l-etyl-7-metyl-4-okso-l,4-dihydro-1, 8-.naf tyr idin-3-karboksylsyre smelter ved 227-228°C , utbytte 87 %.
EKSEMPEL 5
1 g l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbo-nylmetyl-quinolinium-jodid kokes under tilbakeløp i 30 ml 4%'ig natriumhydroksydoppløsning. Reaksjonsblandingen surgjøres med saltsyre og den presipiterte l-etyl-7-metyl-4-okso-l,4-dihydro-1,8-naftyridin-3-karboksylsyre filtreres fra, smp. 227-228°C,
utbytte 83 %.
EKSEMPEL 6
1 g l-etyl-7-metyl-4-okso-l,4-dihydro-l,8-naftyridin-3-karbo-nylmetyl-isoquinolinium-jodid kokes under tilbakeløp i 30 ml av en 4%'ig natriumhydroksydoppløsning. Reaksjonsblandingen sur-
gjøres med saltsyre og den presipiterte l-etyl-7-metyl-4-okso-1,4-dihydro-l,8-naftyridin-3-karboksylsyre filtreres fra, smp.
228-229°C.
Claims (1)
- Fremgangsmåte ved fremstilling av l-alkyl-7-metyl-4-okso-1,4-dihydro-l,8-naftyridin-3-karboksylsyrer av den generelle formel (I)hvor alkyl betegner alkyl med 1-6 C-atomer, karakterisert ved at en forbindelse av den generelle formel (II) hvor Y er en pyridinyl-, picolinyl-, quinolyl- eller isoquinolylgruppe, X er et halogenidanion, og alkyl har ovenfor nevnte betydning, hydrolyseres i nærvær av et alkalimetallhydroksyd eller trialkylaminer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU73CI00001430A HU171561B (hu) | 1973-12-29 | 1973-12-29 | Sposob poluchenija proizvodnykh 1,8-naftiridina |
| HU74CI00001522A HU171869B (hu) | 1974-01-17 | 1974-12-05 | Novyj sposob poluchenija proizvodnykh 1,8-naftiridina |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO744717L NO744717L (no) | 1975-07-28 |
| NO140498B true NO140498B (no) | 1979-06-05 |
| NO140498C NO140498C (no) | 1979-09-12 |
Family
ID=26318398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO744717A NO140498C (no) | 1973-12-29 | 1974-12-27 | Fremgangsmaate ved fremstilling av 1,8-naftyridin-derivater |
Country Status (10)
| Country | Link |
|---|---|
| BG (1) | BG23749A3 (no) |
| CA (1) | CA1051434A (no) |
| CH (1) | CH612967A5 (no) |
| DD (1) | DD115904A5 (no) |
| DK (1) | DK677574A (no) |
| ES (1) | ES433692A1 (no) |
| FI (1) | FI375674A7 (no) |
| NL (2) | NL161452C (no) |
| NO (1) | NO140498C (no) |
| SE (1) | SE419862B (no) |
-
1974
- 1974-12-23 DK DK677574A patent/DK677574A/da not_active Application Discontinuation
- 1974-12-24 CH CH1730674A patent/CH612967A5/de not_active IP Right Cessation
- 1974-12-27 CA CA217,000A patent/CA1051434A/en not_active Expired
- 1974-12-27 FI FI3756/74A patent/FI375674A7/fi unknown
- 1974-12-27 NL NL7416927.A patent/NL161452C/xx not_active IP Right Cessation
- 1974-12-27 SE SE7416322A patent/SE419862B/xx unknown
- 1974-12-27 NO NO744717A patent/NO140498C/no unknown
- 1974-12-29 ES ES433692A patent/ES433692A1/es not_active Expired
- 1974-12-30 BG BG028616A patent/BG23749A3/xx unknown
- 1974-12-30 DD DD183436A patent/DD115904A5/xx unknown
-
1979
- 1979-01-18 NL NL7900400A patent/NL7900400A/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ES433692A1 (es) | 1977-02-16 |
| NL161452C (nl) | 1980-02-15 |
| FI375674A7 (no) | 1975-06-30 |
| NO744717L (no) | 1975-07-28 |
| CH612967A5 (en) | 1979-08-31 |
| NO140498C (no) | 1979-09-12 |
| DD115904A5 (no) | 1975-10-20 |
| NL7900400A (nl) | 1979-05-31 |
| DK677574A (no) | 1975-09-08 |
| NL7416927A (nl) | 1975-07-01 |
| SE7416322L (no) | 1975-06-30 |
| CA1051434A (en) | 1979-03-27 |
| SE419862B (sv) | 1981-08-31 |
| BG23749A3 (bg) | 1977-10-12 |
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