JPS5936637B2 - 6-nitro-1,8-naphthyridine derivative - Google Patents
6-nitro-1,8-naphthyridine derivativeInfo
- Publication number
- JPS5936637B2 JPS5936637B2 JP51000197A JP19776A JPS5936637B2 JP S5936637 B2 JPS5936637 B2 JP S5936637B2 JP 51000197 A JP51000197 A JP 51000197A JP 19776 A JP19776 A JP 19776A JP S5936637 B2 JPS5936637 B2 JP S5936637B2
- Authority
- JP
- Japan
- Prior art keywords
- naphthyridine
- oxo
- carboxylic acid
- ethanol
- ethyl
- 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.)
- Expired
Links
- LWCIMZAHHYGUGQ-UHFFFAOYSA-N 3-nitro-1,8-naphthyridine Chemical class N1=CC=CC2=CC([N+](=O)[O-])=CN=C21 LWCIMZAHHYGUGQ-UHFFFAOYSA-N 0.000 title 1
- -1 pyrrolidino, piperidino, morpholino, piperazino Chemical group 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- GQARCBBQVGDAGN-UHFFFAOYSA-N ClC1=C(C=C2C(C(=CN(C2=N1)CC)C(=O)OCC)=O)[N+](=O)[O-] Chemical compound ClC1=C(C=C2C(C(=CN(C2=N1)CC)C(=O)OCC)=O)[N+](=O)[O-] GQARCBBQVGDAGN-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- DJTCBYANOZVABJ-UHFFFAOYSA-N ethyl 1-ethyl-6-nitro-4-oxo-1,8-naphthyridine-3-carboxylate Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)C(C(=O)OCC)=CN(CC)C2=N1 DJTCBYANOZVABJ-UHFFFAOYSA-N 0.000 description 1
- PIHWQJBFCRABCQ-UHFFFAOYSA-N ethyl 2-oxo-1h-1,8-naphthyridine-3-carboxylate Chemical compound C1=CN=C2NC(=O)C(C(=O)OCC)=CC2=C1 PIHWQJBFCRABCQ-UHFFFAOYSA-N 0.000 description 1
- YYBVNDNVINYCTR-UHFFFAOYSA-N ethyl 7-(4-chloroanilino)-1-ethyl-6-nitro-4-oxo-1,8-naphthyridine-3-carboxylate Chemical compound [O-][N+](=O)C=1C=C2C(=O)C(C(=O)OCC)=CN(CC)C2=NC=1NC1=CC=C(Cl)C=C1 YYBVNDNVINYCTR-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
- WWECJGLXBSQKRF-UHFFFAOYSA-N n,n-dimethylformamide;methanol Chemical compound OC.CN(C)C=O WWECJGLXBSQKRF-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
Description
【発明の詳細な説明】
本発明は優れた抗トリコモナス作用を示す新規な６−ニ
トロー７一置換アミノー１・８−ナフチリジンカルボン
酸エステル誘導体に関するものであり、その製法を反応
式で示せば、次の通りである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel 6-nitro-7 monosubstituted amino-1,8-naphthyridine carboxylic acid ester derivative that exhibits excellent anti-trichomoniacal activity. It is as follows.
（Ｉ）
（式中Ｒおよびｋはそれぞれ、水素、低級アルキル、ヒ
ドロキシ低級アルキル、ジ低級アルキルアミノ低級アル
キル、シクロアルキル、フエニル、ハロゲノフエニルま
たは低級アルコキシフエニルを意味するか、または二〕
Ｎ−でピロリジノ、ピペリジ人モルポリ人ピペラジノま
たは低級アルキルピペラジノを意味する。(I) (wherein R and k each mean hydrogen, lower alkyl, hydroxy lower alkyl, di-lower alkylamino lower alkyl, cycloalkyl, phenyl, halogenophenyl or lower alkoxyphenyl, or
N- means pyrrolidino, piperidino, morporizino, or lower alkylpiperazino.
Ｒ１およびＲ３はそれぞれ低級アルキルを意味する。す
なわち、本発明は、（）と（）を反応させて得られる６
−ニトローメ置換アミノ−１アルキル−１・４−ジヒト
ロー４−オキソ一１・８−ナフチリジン一３−カルボン
酸アルキルエステル（１）に関する。R1 and R3 each mean lower alkyl. That is, the present invention provides 6 obtained by reacting () and ().
-Nitrome-substituted amino-1-alkyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid alkyl ester (1).
（１）を製造するには、通常は、（）および（）を溶媒
に溶解または懸濁させ、加熱して反応させる。To produce (1), usually () and () are dissolved or suspended in a solvent and reacted by heating.
溶媒としては、メタノール、エタノール、ジメチルホル
ムアミド、ジメチルスルホキサイドなどが用いられるが
、この他にも、（）および（）と反応せず、しかも、（
）および（）を若干でも溶解するものであればよい。Examples of solvents that can be used include methanol, ethanol, dimethylformamide, and dimethyl sulfoxide.
) and () may be dissolved at least slightly.
反応条件としては、室温〜１５０℃の温度で５分乃至１
０時間反応させればよく、試剤等の種類によつで若干異
るが、一般に反応は極めて好収率で行われる。The reaction conditions are room temperature to 150°C for 5 minutes to 1 hour.
The reaction may be carried out for 0 hours, and the reaction is generally carried out in an extremely good yield, although this may vary slightly depending on the type of reagent, etc.
上述のようにして製造される化合物（１）はすべて新規
化合物であり、優れた抗トリコモナス作用を示す。All of the compounds (1) produced as described above are new compounds and exhibit excellent anti-trichomoniacal activity.
例えば１−エチル−６−ニトロー７（ｐ−クロロアニリ
ノ）−１・４−ジヒトロー４−オキソ一１・８−ナフチ
リジン一３−カルボン酸エチル（Ａ）、１−エチル−６
−ニトローー１・８−ナフチリジン一３−カルボン酸エ
チル（Ｂ）の抗トリコモナス作用を、抗トリコモナス剤
として知られているメトロニダゾール（Ｃ）を対照とし
て、浅見培地を用いて試験した結果を示すと次表の通り
である。以下、実施例により、本発明に係る化合物の製
法を記す。For example, ethyl 1-ethyl-6-nitro-7(p-chloroanilino)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate (A), 1-ethyl-6
-The results of testing the anti-trichomoniacal effect of ethyl nitro-1,8-naphthyridine-3-carboxylate (B) using Asami medium with metronidazole (C), which is known as an anti-trichomoniacal agent, as a control are shown below. As shown in the table. Hereinafter, the method for producing the compound according to the present invention will be described with reference to Examples.
尚、本発明の原料化合物はすべて新規化合物であり、そ
の製法の１例を参考例に示す。All of the raw material compounds of the present invention are new compounds, and one example of their production method is shown in Reference Example.
参考例
１−エチルーメアミノ一１・４−ジヒトロー４−オキソ
一１・８−ナフチリジン一３−カルボン酸２５ｙを濃硫
酸２６０ｍ１に溶解し、これに濃硝酸２６ｍｊを加えて
８０℃で２時間加熱する。Reference Example 1 - 25y of ethylumeamino-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid is dissolved in 260ml of concentrated sulfuric acid, 26mj of concentrated nitric acid is added thereto, and the mixture is heated at 80°C for 2 hours.
反応混合物を氷水にあけ、析出晶を濾取してジメチルホ
ルムアミド−メタノールの混液から再結晶すれば淡黄色
針状晶として融点２７５〜２７７℃の１−エチル−６−
ニトローメハイドロキシ一１・４−ジヒトロー４−オキ
ソ一１・８−ナフチリジン一３−カルボン酸２８．７ｙ
（９６．０％）を得る。このようにして得た１−エチル
−６−ニトロメハイドロキシ一１・４−ジヒトロー４−
オキソ一１・８−ナフチリジン一３−カルボン酸１０．
５７および塩化チオニル３０ｍ１の混合物を室温で１６
時間攪拌する。反応混合物をエタノール３００ｍ１にあ
け、室温に３０分間放置後、減圧下にエタノールを濃縮
する。析出晶を濾取し、クロロホルム−メタノールの混
液から再結晶すれば、淡黄色針状晶として融点２３９〜
２４１℃の１−エチル−６−ニトローメハイドロキシ一
１・４−ジヒトロー４−オキソ一１・８−ナフチリジン
一３−カルボン酸エチルエステル８．８０ｆ７（７５．
８％）を得る。このようにして得た１−エチル−６−ニ
トロメハイドロキシ一１・４−ジヒトロー４−オキソ一
１・８−ナフチリジン一３−カルボン酸エチルエステル
１５．０７およびオキシ塩化リン８０ｍｊの混合物を８
０〜９０℃で２時間攪拌する。The reaction mixture was poured into ice water, and the precipitated crystals were collected by filtration and recrystallized from a dimethylformamide-methanol mixture to give 1-ethyl-6- as pale yellow needle crystals with a melting point of 275-277°C.
Nitromehydroxy-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid 28.7y
(96.0%). Thus obtained 1-ethyl-6-nitromehydroxy-1,4-dihythro-4-
Oxo-1,8-naphthyridine-3-carboxylic acid 10.
A mixture of 57 and 30 ml of thionyl chloride was added to 16
Stir for an hour. The reaction mixture was poured into 300 ml of ethanol, and after standing at room temperature for 30 minutes, the ethanol was concentrated under reduced pressure. If the precipitated crystals are collected by filtration and recrystallized from a chloroform-methanol mixture, pale yellow needle crystals with a melting point of 239~
1-Ethyl-6-nitromehydroxy-1,4-dihythro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester at 241°C 8.80f7 (75.
8%). A mixture of 15.07 g of 1-ethyl-6-nitromehydroxy-1,4-dihythro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester thus obtained and 80 mj of phosphorus oxychloride was added to 80 mj of phosphorus oxychloride.
Stir at 0-90°C for 2 hours.
冷後、反応混合物を氷水にあけ、炭酸水素ナトリウムで
中和したのち、生成物をクロロホルムで抽出する。抽出
液を水洗し、乾燥したのち、減圧下に濃縮すると無色針
状晶として融点１９５〜１９７℃の１エチル−６−ニト
ローメクロロ一１・４−ジヒトロー４−オキソ一１・８
−ナフチリジン一３−カルボン酸エチルエステル１２．
８Ｖ（８０．４％）を得る。実施例 １
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ｙおよびｐ−クロロアニリン２
．６８ｙをジメチルホルムアミド５０ｍ１！，に加えて
８０℃で１時間攪拌する。After cooling, the reaction mixture was poured into ice water, neutralized with sodium bicarbonate, and the product was extracted with chloroform. The extract was washed with water, dried, and concentrated under reduced pressure to give colorless needle crystals with a melting point of 195 to 197°C.
-Naphthyridine-3-carboxylic acid ethyl ester 12.
Obtain 8V (80.4%). Example 1 1-ethyl-6-nitromechloro-1,4-dihytro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.26y and p-chloroaniline 2
．． 68y with 50ml of dimethylformamide! , and stirred at 80°C for 1 hour.
ジメチルホルムアミドを減圧留去し、残渣をクロロホル
ムに溶解し、水洗、乾燥後、クロロホルムを留去し、残
渣をクロロホルム−エタノールの混液から再結晶すれば
、融点２２２〜２２４℃の１−エチル−６−ニトロ−７
−（ｐ−クロロアニリノ）−１・４−ジヒトロー４−オ
キソ一１・８−ナフチリジン一３−カルボン酸エチルエ
ステル３．５６ｙ（８５．４％）を得る。実施例 ２
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ｙおよびｐ−メトキシアニリン
２．５８Ｖをジメチルホルムアミド５０ｍｉに加えて以
下実施例１に示したと同様に処理すると融点２０３〜２
０５℃の１−エチル−６−ニトロ−７−（ｐ−メトキシ
アニリノ）−１・４−ジヒトロー４−オキソ一１・８−
ナフチリジン一３−カルボン酸エチルエステル３．４６
Ｖ（８４．１％）を得る。Dimethylformamide is distilled off under reduced pressure, the residue is dissolved in chloroform, washed with water, dried, chloroform is distilled off, and the residue is recrystallized from a chloroform-ethanol mixture to obtain 1-ethyl-6 with a melting point of 222-224°C. -Nitro-7
-(p-chloroanilino)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.56y (85.4%) is obtained. Example 2 3.26y of 1-ethyl-6-nitromechloro-1,4-dihytho-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester and 2.58V of p-methoxyaniline were added to 50mi of dimethylformamide. When treated in the same manner as shown in Example 1, the melting point was 203-2.
1-ethyl-6-nitro-7-(p-methoxyanilino)-1,4-dihythro-4-oxo-1,8- at 05°C
Naphthyridine-3-carboxylic acid ethyl ester 3.46
V (84.1%) is obtained.
実施例 ３
１−エチル−６−ニトロ−７−クロロ−１・４−ジヒト
ロー４−オキソ一１・８−ナフチリジン一３−カルボン
酸エチルエステル３．２６Ｖおよびシクロヘキシルアミ
ン２．１０ｙをエタノール５０ｍ１に加えて８０℃に１
０分間攪拌する。Example 3 3.26 V of 1-ethyl-6-nitro-7-chloro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester and 2.10 y of cyclohexylamine were added to 50 ml of ethanol. 1 at 80℃
Stir for 0 minutes.
エタノールを減圧留去し、残渣をクロロホルムに溶解し
、水洗、乾燥後、クロロホルムを留去し、残渣をエタノ
ールから再結晶すれば融点２１５〜２１６℃の１−エチ
ル−６−ニトローメシクロヘキシルアミノ一１・４−ジ
ヒトロー４−オキソ一１・８−ナフチリジン一３−カル
ボン酸エチルエステル３．２０１（８２．５％）を得る
。実施例 ４
１−エチル−６＝ニトローメクロロ＝ｌ・４−ツヒドロ
一４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ｙおよびβ−ジエチルアミノエ
チルアミン２．４４Ｖをエタノール５０ｍ１に加えて５
０℃に１．５時間攪拌したのち、実施例３に示したと同
様に処理し、エタノールから再結晶すれば、融点１５９
〜１６１℃の１−エチル−６−ニトローヨ黶β−ジエチ
ルアミノエチルアミノ）−１・４−ジヒドロ＝４＝オキ
ソ一１・８−ナフチリジン一３−カルボン酸エチルエス
テル４．００Ｖ（９９％）を得る。Ethanol is distilled off under reduced pressure, the residue is dissolved in chloroform, washed with water, dried, chloroform is distilled off, and the residue is recrystallized from ethanol to give 1-ethyl-6-nitromecyclohexylamino with a melting point of 215-216°C. 3.201 (82.5%) of -1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester are obtained. Example 4 3.26y of 1-ethyl-6-nitromechloro-l-4-tuhydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester and 2.44V of β-diethylaminoethylamine were added to 50ml of ethanol. 5
After stirring at 0°C for 1.5 hours, the same treatment as shown in Example 3 and recrystallization from ethanol give a melting point of 159.
Obtain 4.00 V (99%) of 1-ethyl-6-nitro-(β-diethylaminoethylamino)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester at ~161°C. .
実施例 ５
１−エチル−６−ニトロ−７−クロロ−１・４−ジヒト
ロー４−オキソ一１・８＝ナフチリジン一３＝カルボン
酸エチルエステル３．２６ｙおよびエタノールアミン１
．２２ｙをエタノール５０ｍ１に加えて、以下実施例３
に示したと同様に処理し、クロロホルム−エタノールの
混液から再結晶すれば、融点２２３〜２２５℃の１−エ
チル−６−ニトローヨ黶β−ハイドロキシエチルアミノ
）一１・４−ジヒトロー４−オキソ一ｌ・８−ナフチリ
ジン一３−カルボン酸エチルエステル３．２２Ｖ（９２
．０％）を得る。Example 5 1-ethyl-6-nitro-7-chloro-1,4-dihydro-4-oxo-1,8=naphthyridine-3=carboxylic acid ethyl ester 3.26y and ethanolamine 1
．． 22y was added to 50 ml of ethanol, and the following example 3 was prepared.
If the treatment is performed in the same manner as shown in , and recrystallized from a mixture of chloroform and ethanol, 1-ethyl-6-nitro (β-hydroxyethylamino)-1,4-dihydro-4-oxo-1 with a melting point of 223-225°C is obtained.・8-Naphthyridine-3-carboxylic acid ethyl ester 3.22V (92
．． 0%).
実施例 ６
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ＶおよびＮ−シクロヘキシル−
Ｎ−メチルアミン２．２６Ｖをエタノール５０ｍ１に加
えて、以下実施例３に示したと同様に処理し、ベンゼン
一石油エーテルの混液から再結晶すれば、融点１５９〜
１６１℃の１−エチル−６−ニトローヨ黶Ｎ−シクロヘ
キシル−Ｎ−メチルアミノ）−１・４−ジヒトロー４−
オキソ一１・８−ナフチリジン一３−カルボン酸エチル
エステル３．９８ｔ（９９．０％）を得る。Example 6 1-Ethyl-6-nitromechloro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.26V and N-cyclohexyl-
When 2.26V of N-methylamine is added to 50ml of ethanol, treated in the same manner as shown in Example 3, and recrystallized from a mixture of benzene and petroleum ether, the melting point is 159~
1-ethyl-6-nitro-(N-cyclohexyl-N-methylamino)-1,4-dihydro-4- at 161°C
3.98 t (99.0%) of oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester is obtained.
実施例 ７
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ｙおよびＮ−エチルエタノール
アミン１．７８ｒをエタノール５０ｍ２に加えて、以下
実施例３に示したと同様に処理し、エタノールから再結
晶すれば融点１７３〜１７４℃の１−エチル−６−ニト
ローミノ）−１・４−ジヒトロー４−オキソ一１・８一
ナフチリジン一３−カルボン酸エチルエステル３．６８
ｆ（９７．１％）を得る。Example 7 3.26y of 1-ethyl-6-nitromechloro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester and 1.78r of N-ethylethanolamine were added to 50 m2 of ethanol. , treated in the same manner as shown in Example 3 and recrystallized from ethanol to give 1-ethyl-6-nitromino)-1,4-dihydro-4-oxo-1,8-naphthyridine-3 with a melting point of 173-174°C. -carboxylic acid ethyl ester 3.68
We obtain f (97.1%).
実施例 ８
１−エチルニ６−ニトローメクロロ一１・４ジヒトロー
４−オキソ一１・８−ナフチリジン一３−カルボン酸エ
チルエステル３．２６７およびジエタノールアミン２．
１０７をエタノール５０ｍ１に加えて、以下実施例３に
示したと同様に処理し、エタノールから再結晶すれば、
融点１９４〜１９６℃の１−エチル−６−ニトローヨ黶
Ｎ・Ｎ−ジ一β−ハイドロキシエチルアミノ）−１・４
−ジヒトロー４−オキソ一１・８−ナフチリジン一３−
カルボン酸エチルエステル３．２９７（８３．５％）を
得る。Example 8 1-Ethyl di-6-nitromechloro-1,4-dihythro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.267 and diethanolamine 2.
107 is added to 50 ml of ethanol, treated in the same manner as shown in Example 3 below, and recrystallized from ethanol.
1-ethyl-6-nitrofluoriN-N-di-β-hydroxyethylamino)-1.4 with a melting point of 194-196°C
-dihythro-4-oxo-1,8-naphthyridine-3-
3.297 (83.5%) of carboxylic acid ethyl ester are obtained.
実施例 ９
１−エチル−６−ニトローメクロロ一１・４ジヒトロー
４−オキソ一１・８−ナフチリジン３−カルボン酸工壬
ルエス子ル３９らｇ艙上Ｙドピロリジン１．４２ｆ７を
エタノール５０ｍ１に加えて７０℃に１時間加熱し、以
下、実施例３に示したと同様に処理し、ベンゼンから再
結晶すれば融点１９９〜２０１℃の１−エチル−６−ニ
トロー１・８−ナフチリジン一３−カルボン酸エチルエ
ステル３．５３ｆ（９８．０％）を得る。Example 9 1-Ethyl-6-nitromechloro-1,4-dimethyl-4-oxo-1,8-naphthyridine 3-carboxylic acid 39 g 1.42 f7 of Y dopyrrolidine was added to 50 ml of ethanol and 70 ℃ for 1 hour, followed by treatment in the same manner as shown in Example 3, and recrystallization from benzene yields ethyl 1-ethyl-6-nitro-1,8-naphthyridine-3-carboxylate with a melting point of 199-201℃. Ester 3.53f (98.0%) is obtained.
実施例 １０
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ｙおよびピペリジン１．７０ｙ
をエタノール５０ｍ１に加えて５０℃に４５分間加熱し
、以下実施例３に示したと同様に処理し、エタノールか
ら再結晶すれば融点１７３〜１７５℃の１−エチル−６
−ニトローメピペリジノ一１・４−ジヒトロー４−オキ
ソ一１・８−ナフチリジン一３−カルボン酸エチルエス
テル２．１３ｙ（５７．３％）を得る。Example 10 1-ethyl-6-nitromechloro-1,4-dihytro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.26y and piperidine 1.70y
was added to 50 ml of ethanol, heated to 50°C for 45 minutes, treated in the same manner as shown in Example 3, and recrystallized from ethanol to obtain 1-ethyl-6 with a melting point of 173-175°C.
-Nitromepiperidino-1,4-dihytro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 2.13y (57.3%) is obtained.
実施例 １１
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ｒおよびモルホリン１．７４ｙ
をエタノール５０ｍ１に加えて７０℃に１時間加熱し、
以下実施例３に示したと同様に処理し、エタノールから
再結晶すれば融点１９３〜１９４℃の１−エチル−６−
ニトロー１・８−ナフチリジン一３−カルボン酸エチル
エステル３．４６ｙ（９２．０％）を得る。Example 11 1-Ethyl-6-nitromechloro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.26r and morpholine 1.74y
was added to 50 ml of ethanol and heated to 70°C for 1 hour.
The following treatment is carried out in the same manner as shown in Example 3, and when recrystallized from ethanol, 1-ethyl-6-
Nitro 1,8-naphthyridine-3-carboxylic acid ethyl ester 3.46y (92.0%) is obtained.
実施例 １２
１−エチル−６−ニトローメクロロ一１・４一ジヒドロ
一４−オキソ一１・８−ナフチリジン一３−カルボン酸
エチルエステル３．２６ｒおよびピペラジン１．７２７
をエタノール５０ｍ１に加えて８０℃に２時間加熱し以
下実施例３に示したと同様に処理し、クロロホルム−エ
タノールの混液から再結晶すれば融点２０３〜２０５℃
の１−エチル−６−[メCトローメピペラジノ一１・４−
ジヒトロー４−オキソ一１・８−ナフチリジン一３一カ
ルボン酸エチルエステル１．３６７（３６．４％）を得
る。Example 12 1-Ethyl-6-nitromechloro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.26r and piperazine 1.727
is added to 50 ml of ethanol, heated to 80°C for 2 hours, treated in the same manner as shown in Example 3, and recrystallized from a chloroform-ethanol mixture to obtain a melting point of 203-205°C.
1-Ethyl-6-[methlomepiperazino-1,4-
1.367 (36.4%) of dihythro-4-oxo-1,8-naphthyridine-3-monocarboxylic acid ethyl ester is obtained.
元素分析値 Ｃｌ７Ｈ２ｌＮ５Ｏ５
計算値 Ｃ５４．３９、Ｈ５．６４、Ｎｌ８．６６実験
値 Ｃ５４．３６、Ｈ５．７４、Ｎｌ８．３２実施例
１３
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジンー３−カルボン酸
エチルエステル３．２６ｙおよびＮ−メチルピペラジン
２．００７をエタノール５０ｍ１に加えて５０℃に２時
間加熱し、以下実施例３に示したと同様に処理し、エタ
ノール一石油エーテルから再結晶すれば融点１７４〜１
７６℃の１−エチル−６−ニトローヨ黶Ｎ−メチルピペ
ラジノ）−１・４−ジヒトロー４−オキソ一１・８−ナ
フチリジン一３−カルボン酸エチルエステル１．９３７
（４９．６％）を得る。Elemental analysis value Cl7H2lN5O5 Calculated value C54.39, H5.64, Nl8.66 Experimental value C54.36, H5.74, Nl8.32 Example
13 Add 3.26y of 1-ethyl-6-nitromechloro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester and 2.007y of N-methylpiperazine to 50ml of ethanol and heat to 50°C for 2 hours. The melting point is 174 to 1 when heated for an hour, treated in the same manner as shown in Example 3, and recrystallized from ethanol and petroleum ether.
1-ethyl-6-nitro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester at 76°C 1.937
(49.6%).
元素分析値 Ｃｌ８Ｈ２３Ｎ５Ｏ５
計算値 Ｃ５５．５２、Ｈ５，９２、Ｎｌ７．９９実験
値 Ｃ５５．８Ｏ，．Ｈ６．Ｏ２、Ｎｌ７．７４実施例
１４
１−エチル−６−ニトローメクロロ一１・４−ジヒトロ
ー４−オキソ一１・８−ナフチリジンー３−カルボン酸
エチルエステル３．２６ｙおよびＮ−メチルアニリン２
．１４７をエタノール５０ｍ１に加えて９０℃に１時間
加熱し、以下実施例３に示したと同様に処理し、エタノ
ールから再結晶すれば融点１８１〜１８３℃の１−エチ
ル−６−ニトローヨ黶Ｎ−メチルアニリノ）−１・４−
ジヒトロー４−オキソ一１・８−ナフチリジン一３一カ
ルボン酸エチルエステル２．９６７（７４．７％）を得
る。Elemental analysis value Cl8H23N5O5 Calculated value C55.52, H5,92, Nl7.99 Experimental value C55.8O,. H6. O2, Nl 7.74 Example 14 1-ethyl-6-nitromechloro-1,4-dihythro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.26y and N-methylaniline 2
．． 147 was added to 50 ml of ethanol, heated to 90°C for 1 hour, and then treated in the same manner as shown in Example 3. If recrystallized from ethanol, 1-ethyl-6-nitroyo-N-methylanilino with a melting point of 181-183°C was obtained. )-1・4-
2.967 (74.7%) of dihythro-4-oxo-1,8-naphthyridine-3-monocarboxylic acid ethyl ester is obtained.
元素分析値 Ｃ２ＯＨ２ＯＮ４Ｏ５
計算値 Ｃ６Ｏ．６Ｏ，．Ｈ５．Ｏ９、Ｎｌ４．ｌ４実
験値 Ｃ６Ｏ．５９、Ｈ５．Ｏｌ、Ｎｌ３．９５実施例
１５
１−エチル−６−ニトローメクロロ一１・４ジヒトロー
４−オキソ一１・８−ナフチリジンー３−カルボン酸エ
チルエステル３．２６７およびジエチルアミン７．３７
をエタノール５０ｍ１に加えて８０℃に２時間加熱し、
以下実施例３に示したと同様に処理し、クロロホルム−
エタノールの混液から再結晶すれば融点１２６〜１２８
℃の１−エチル−６−ニトローメジエチルアミノ一１・
４−ジヒトロー４−オキソ一１・８−ナフチリジン一３
−カルボン酸エチルエステル３．４０７（９４．０％）
を得る。Elemental analysis value C2OH2ON4O5 Calculated value C6O. 6O,. H5. O9, Nl4. l4 Experimental value C6O. 59, H5. Ol, Nl 3.95 Example 15 1-Ethyl-6-nitromechloro-1,4-dihythro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 3.267 and diethylamine 7.37
was added to 50 ml of ethanol and heated to 80°C for 2 hours,
The following treatment was carried out in the same manner as shown in Example 3, and chloroform-
If recrystallized from a mixture of ethanol, the melting point will be 126-128.
1-ethyl-6-nitromediethylamino-1 at °C
4-dihythro-4-oxo-1,8-naphthyridine-3
-Carboxylic acid ethyl ester 3.407 (94.0%)
get.
元素分析値 Ｃｌ７Ｈ２２Ｎ４Ｏ５
計算値 Ｃ５６．３４、Ｈ６．ｌ２、Ｎｌ５．４６実験
値 Ｃ５６．５３、Ｈ６．ｌ３、Ｎｌ５．２Ｏ実施例
１６
エタノール５０ｍｅにアンモニアガス１．７ｙを導入し
、これに１−エチル−６−ニトローメクロロ一１・４−
ジヒトロー４−オキソ一１・８−ナフチリジン一３−カ
ルボン酸エチルエステル３．２６ｙを加えて６０℃に２
時間加熱し、以下実施例３に示したと同様に処理し、水
から再結晶すれば、融点２６２〜２６４℃の１−エチル
−６−ニトローメアミノ一１・４−ジヒトロー４−オキ
ソ１・８−ナフチリジン一３−カルボン酸エチルエステ
ル２．０９ｙ（６８．３％）を得る。Elemental analysis value Cl7H22N4O5 Calculated value C56.34, H6. l2, Nl5.46 experimental value C56.53, H6. l3, Nl5.2O example
16 Introduce 1.7y of ammonia gas into 50me of ethanol, and add 1-ethyl-6-nitromechloro-1,4-
Add 3.26y of dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester and heat to 60℃ for 2 hours.
1-ethyl-6-nitromeamino-1,4-dihydro-4-oxo-1,8-naphthyridine with a melting point of 262-264°C. 2.09y (68.3%) of mono-3-carboxylic acid ethyl ester is obtained.
元素分析値 Ｃｌ３Ｈｌ４Ｎ４Ｏ５Elemental analysis value Cl3Hl4N4O5
Claims (1)
ヒドロキシ低級アルキル、ジ低級アルキルアミノ低級ア
ルキル、シクロアルキル、フェニル、ハロゲノフエニル
または低級アルコキシフェニルを意味するか、または▲
数式、化学式、表等があります▼でピロリジノ、ピペリ
ジノ、モルホリノ、ピペラジノまたは低級アルキルピペ
ラジノを意味する。 Ｒ＿１およびＲ＿３はそれぞれ低級アルキルを意味する
。）で表わされる化合物。[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R and R' are hydrogen, lower alkyl,
means hydroxy lower alkyl, di-lower alkylamino lower alkyl, cycloalkyl, phenyl, halogenophenyl or lower alkoxyphenyl, or ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ means pyrrolidino, piperidino, morpholino, piperazino or lower alkylpiperazino. R_1 and R_3 each mean lower alkyl. ).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51000197A JPS5936637B2 (en) | 1976-01-01 | 1976-01-01 | 6-nitro-1,8-naphthyridine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51000197A JPS5936637B2 (en) | 1976-01-01 | 1976-01-01 | 6-nitro-1,8-naphthyridine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5283590A JPS5283590A (en) | 1977-07-12 |
| JPS5936637B2 true JPS5936637B2 (en) | 1984-09-05 |
Family
ID=11467257
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51000197A Expired JPS5936637B2 (en) | 1976-01-01 | 1976-01-01 | 6-nitro-1,8-naphthyridine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5936637B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR223983A1 (en) * | 1978-08-25 | 1981-10-15 | Dainippon Pharmaceutical Co | A PROCEDURE FOR PREPARING 6-HALOGEN-4-OXO-7- (1-PIPERAZINYL) -1,8-NAFTIRIDIN-3-CARBOXYLIC ACID DERIVATIVES |
-
1976
- 1976-01-01 JP JP51000197A patent/JPS5936637B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5283590A (en) | 1977-07-12 |
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