JPS6042797B2 - Furoquinoline derivatives - Google Patents
Furoquinoline derivativesInfo
- Publication number
- JPS6042797B2 JPS6042797B2 JP7060878A JP7060878A JPS6042797B2 JP S6042797 B2 JPS6042797 B2 JP S6042797B2 JP 7060878 A JP7060878 A JP 7060878A JP 7060878 A JP7060878 A JP 7060878A JP S6042797 B2 JPS6042797 B2 JP S6042797B2
- Authority
- JP
- Japan
- Prior art keywords
- quinoline
- oxazino
- carboxylic acid
- compound
- furo
- 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
- NBIQERZFHYWUCH-UHFFFAOYSA-N furo[2,3-h]quinoline Chemical class C1=CN=C2C(C=CO3)=C3C=CC2=C1 NBIQERZFHYWUCH-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 16
- VXGYRCVTBHVXMZ-UHFFFAOYSA-N quinoline-6-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CC=C21 VXGYRCVTBHVXMZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims 3
- 150000003248 quinolines Chemical class 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- -1 alkaline earth metal salts Chemical class 0.000 description 9
- 238000000921 elemental analysis Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CFBCZETZIPZOGW-UHFFFAOYSA-N 1-benzofuran-4-ol Chemical compound OC1=CC=CC2=C1C=CO2 CFBCZETZIPZOGW-UHFFFAOYSA-N 0.000 description 2
- AYXIMXFVNFTMKO-UHFFFAOYSA-N 4-hydroxy-1-benzofuran-6-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C=COC2=C1 AYXIMXFVNFTMKO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OAKWOXQUACOWHQ-UHFFFAOYSA-N 2-nitro-1-benzofuran-4-ol Chemical compound OC1=CC=CC2=C1C=C([N+]([O-])=O)O2 OAKWOXQUACOWHQ-UHFFFAOYSA-N 0.000 description 1
- XNDZQQSKSQTQQD-UHFFFAOYSA-N 3-methylcyclohex-2-en-1-ol Chemical compound CC1=CC(O)CCC1 XNDZQQSKSQTQQD-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- SVHHAAQTOHCWJX-UHFFFAOYSA-N ethyl quinoline-6-carboxylate Chemical compound N1=CC=CC2=CC(C(=O)OCC)=CC=C21 SVHHAAQTOHCWJX-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- WXXVQWSDMOAHHV-UHFFFAOYSA-N quinoline-7-carboxylic acid Chemical compound C1=CC=NC2=CC(C(=O)O)=CC=C21 WXXVQWSDMOAHHV-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は式 ｏ ＣＯＯＨ ？」Ｒ、（Ｉ） （式中Ｒ゛は低級アルキル基を示す。[Detailed description of the invention] The present invention is based on the formula o COOH ? "R, (I) (In the formula, R represents a lower alkyl group.
）で表わされる２・３−ジヒドロ−３−アルキル− −
オキソ− ７Ｈ−フロ〔２・３−ｇ〕〔１・４〕オキサ
ジノ〔２・３・４−ｉ−ｊ〕キノリン−６−カルボン酸
およびそのアルカリ金属またはアルカリ土類金属塩また
はその１０・１１−ジヒドロ体すなわち２・３．１０．
１１−テトラヒドロ−３−アルキル− −オキソ− ７
Ｈ−フロ〔２・３−ｇ〕〔１・４〕オキサジノ〔２・３
・４−ｉ−ｊ〕キノリン−６−カルボン酸およびそのア
ルカリ金属またはアルカリ土類金属塩に関するものであ
り、これらの化合物は優れた抗菌力を有するものである
。本発明の化合物の製造方法を例を反応式を示して説明
する。) 2,3-dihydro-3-alkyl- -
Oxo-7H-furo[2,3-g][1,4]oxazino[2,3,4-i-j]quinoline-6-carboxylic acid and its alkali metal or alkaline earth metal salts or their 10 and 11 -dihydro form, i.e. 2.3.10.
11-tetrahydro-3-alkyl- -oxo- 7
H-Flo [2.3-g] [1.4] Oxazino [2.3
-4-i-j] This relates to quinoline-6-carboxylic acid and its alkali metal or alkaline earth metal salts, and these compounds have excellent antibacterial activity. The method for producing the compound of the present invention will be explained by showing examples and reaction formulas.
式中Ｒ１、Ｒ２およびＲ３はそれぞれ低級アルキル基を
意味し、Ｘはハロゲン原子を、ＹはＣＯＲもしくはＣ（
０Ｒ）２を意味し、ここでＲは低級アルキル基を意味す
る。In the formula, R1, R2 and R3 each mean a lower alkyl group, X is a halogen atom, and Y is COR or C(
0R)2, where R represents a lower alkyl group.
すなわち、４−ヒドロキシベンゾフランー６−カルボン
酸（■）をニトロ化し、得られる４−ヒドロキシー５−
ニトロベンゾフランー６−カルボン酸（■）を脱炭酸す
るか、または４−ヒドロキシベンゾフラン（■）をニト
ロ化して４−ヒドロキシー５−ニトロベンゾフラン（■
）を製し、これに化合物（■）例えばモノクロルアセト
ンを、炭酸カリ、三級アミン等の脱酸剤の存在下反応さ
せ、ついでラネーニツケル等で接触還元して３ーアルキ
ルー〔１・４〕オキサジノ〔２・３−ｅ〕ベンゾフラン
（■）を製し、これにアルコキシメチレンマロン酸エス
テル（■）を反応させて３−アルキルー４−（２・２−
ジアルコキシカルボニルエテニル）−〔１・４〕オキサ
ジノ〔２・３一ｅ〕ベンゾフラン（■）となし、これを
ポリリン酸もしくはポリリン酸エステル類中で加熱して
閉環させ、２・３−ジヒドロー３−アルキルー７ーオキ
ソー７Ｈ−フロ〔２・３−ｇ〕〔１・４〕オキサジノ〔
２・３●４−１−ｊ〕キノリンー６−カルボン酸エステ
ル（Ｘ）を製し、これを酸または塩基で加水分解すると
目的物（１ａ）が得られる。That is, 4-hydroxybenzofuran-6-carboxylic acid (■) is nitrated to obtain 4-hydroxy-5-
Nitrobenzofuran-6-carboxylic acid (■) is decarboxylated or 4-hydroxybenzofuran (■) is nitrated to produce 4-hydroxy-5-nitrobenzofuran (■).
) is reacted with a compound (■) such as monochloroacetone in the presence of a deoxidizing agent such as potassium carbonate or a tertiary amine, and then catalytically reduced with Raney nickel or the like to obtain 3-alkyl-[1,4]oxazino[ 2.3-e] Prepare benzofuran (■) and react it with alkoxymethylene malonic acid ester (■) to obtain 3-alkyl-4-(2.2-
dialkoxycarbonylethenyl)-[1,4]oxazino[2,31e]benzofuran (■), which is heated in polyphosphoric acid or polyphosphoric acid esters to undergo ring closure, to form 2,3-dihydro3 -Alkyl-7-Oxo-7H-Flo[2.3-g][1.4]Oxazino[
2.3●4-1-j] Quinoline-6-carboxylic acid ester (X) is prepared and hydrolyzed with an acid or base to obtain the target product (1a).
また、化合物（Ｘ）をパラジウム炭等の触媒の存在下接
触還元してテトラヒドロ体（■）を製しこれを酸または
塩基で加水分解すると目的物（Ｉｂ）が得られる。これ
らの目的物は常法により適宜そのアルカリ金属塩または
アルカリ土類金属塩に導いて用いることもできる。本発
明の化合物は、グラム陰性菌およびグラム陽性菌に対し
て優れた抗菌作用を示し、優れた抗菌力を有する化合物
として知られるオキソリン酸特公昭４２−５６６６号公
報、Ｊ．Ｍｅｄ．Ｃｈｅｍ．旦１６０（１９６８））に
比しても優れた効力を示し、オキソリン酸と同等の抗菌
力を有すると報告されている５ーエチルー２●３・５・
８−テトラヒドー８−オキソフロ〔２●３−ｇ〕キノリ
ンー７−カルボン酸（ＣｈｅｍｉｃａｌＡｂｓｔｒａｃ
ｔｓｌｐ７２４９９、ＵＳＰ３７７３７６λ西独特許公
開２０３０８９９ｓ特開昭４７一１０８１号公報）に比
しても優れた効力を有すると推定され、毒性も低く有用
な化合物である。Further, compound (X) is catalytically reduced in the presence of a catalyst such as palladium on charcoal to produce a tetrahydro compound (■), which is then hydrolyzed with an acid or a base to obtain the target compound (Ib). These target compounds can also be used by converting them into alkali metal salts or alkaline earth metal salts as appropriate by conventional methods. The compound of the present invention exhibits excellent antibacterial activity against Gram-negative bacteria and Gram-positive bacteria, and is known as a compound having excellent antibacterial activity, as described in Japanese Patent Publication No. 1982-5666, J. Med. Chem. 5-Ethyl 2●3.5.
8-tetrahydro8-oxofuro[2●3-g]quinoline-7-carboxylic acid (ChemicalAbstrac
It is estimated to have superior efficacy compared to tslp72499, USP377376λ (West German Patent Publication No. 2030899, Japanese Patent Application Laid-open No. 471-1081), and is a useful compound with low toxicity.
次に試験管内抗菌試験データおよび合成実験例を示す。
最小発育阻止濃度（■Ｃ．．ｐｆＩＴｆＬｌ）日本化学
療法学会標準法：平板希釈法（ハートインフユージヨン
寒天培地）接種菌量１ＣＪ′／ｍｌ
培養条件３ｒＣ．．比時間
実施例１
４−ヒドロキシベンゾフランー６−カルボン酸１５．０
ｙを氷酢酸３００ｍ１に懸濁させ、攪拌下に硝酸アルミ
ニウム・９水和物９．１ｙを１時間にわたつて加える。Next, in vitro antibacterial test data and synthetic experiment examples are shown.
Minimum inhibitory concentration (■C..pfITfLl) Japanese Society of Chemotherapy standard method: Plate dilution method (heart infusion agar medium) Inoculum amount 1CJ'/ml Culture conditions 3rC. ．． Ratio time Example 1 4-hydroxybenzofuran-6-carboxylic acid 15.0
y is suspended in 300 ml of glacial acetic acid, and 9.1 y of aluminum nitrate nonahydrate is added over 1 hour while stirring.
この間、内温２０〜２３℃に保つ。更に１時間攪拌した
のち、反応液を氷水にあけて酢酸エチルで抽出する。抽
出液は水洗し、乾燥して濃縮していくと、次第に結晶が
析出してくる。冷時析出晶を濾取し、少量のエーテルで
洗うと融点２３１〜２３３取Ｃ（ｄ）の４−ヒドロキシ
ー５−ニトロベンゾフランー６−カルボン酸６．８ｆが
得られる。元素分析値Ｃ９Ｈ５ＮＯ６として理論値Ｃ４
８．４４、Ｈ２．２巳Ｎ６．２８実験値Ｃ４８．３２、
Ｈ２．３未Ｎ６．Ｏ７上記化合物を６．７ｙをキノリン
７０ｍ１および銅粉６ｆ１を１８０℃に加熱した中には
げしく攪拌しながら加え、更に同温度で１紛間攪拌をつ
づける。During this time, keep the internal temperature at 20-23°C. After stirring for an additional hour, the reaction solution was poured into ice water and extracted with ethyl acetate. When the extract is washed with water, dried, and concentrated, crystals gradually begin to precipitate. The crystals precipitated in the cold are collected by filtration and washed with a small amount of ether to obtain 6.8f of 4-hydroxy-5-nitrobenzofuran-6-carboxylic acid having a melting point of 231 to 233 C(d). Theoretical value C4 as elemental analysis value C9H5NO6
8.44, H2.2 N6.28 experimental value C48.32,
H2.3 not yet N6. O7 6.7y of the above compound was added to 70ml of quinoline and 6f1 of copper powder heated to 180°C with vigorous stirring, and stirring was continued for one powder at the same temperature.
冷後、酢酸エチルを加えて不溶分を濾去し、濾液をへ塩
酸と振とうしてキノリンを除く。有機層は水洗し、乾燥
して溶媒を留去し残査をベンゼンに溶してシリカゲルク
ロマトに付す。ベンゼン溶出分より融点１０７℃の５−
ニトロー４−ヒドロキシベンゾフラン３．１１１が得ら
れる。元素分析値Ｃ８ｌｌ．ＮＯ４として
理論値Ｃ５３．６４、Ｈ２．８ｌ、Ｎ７．８２実験値Ｃ
５３．４２、Ｈ２．９臥Ｎ７．６３上記化合物１．０５
ｑ１炭酸カリ０．８３ｙ１ヨウ化カリ０．２０ｙおよび
モノクロルアセトン１．０ｍｔをアセトン２０ｍ１に加
えて１．５時間還流する。After cooling, ethyl acetate was added, insoluble matter was filtered off, and the filtrate was shaken with hydrochloric acid to remove quinoline. The organic layer is washed with water, dried, the solvent is distilled off, and the residue is dissolved in benzene and subjected to silica gel chromatography. 5- with a melting point of 107℃ from the benzene eluate
3.111 nitro-4-hydroxybenzofuran is obtained. Elemental analysis value C8ll. Theoretical value C53.64, H2.8l, N7.82 experimental value C
53.42, H2.9 N7.63 Above compound 1.05
q1 Potassium carbonate 0.83y1 Potassium iodide 0.20y and monochloroacetone 1.0mt are added to 20ml of acetone and refluxed for 1.5 hours.
不溶分を濾去し、溶媒を留去する。得られる油状残渣は
放置すると固化するのでイソプロピルエーテルを加えて
濾取すると融点７８℃の４−アセトニルオキシー５−ニ
トロベンゾフラン１．１９ｇが得られる。元素分析値Ｃ
ｌｌＨ９ＮＯ５として理論値Ｃ５６．ｌ７、Ｈ３．８Ｃ
）ＳＮ５．９６実験値Ｃ５５．９Ｆ３ｓＨ３．６９ｓＮ
６．Ｏ４上記化合物１．６ｙをエタノール５０ｍｔに溶
かし、ラネーニツケル２ｍ１を加えて常圧接触還元する
。Insoluble matter is filtered off and the solvent is distilled off. The resulting oily residue solidifies when left to stand, so isopropyl ether is added and collected by filtration to obtain 1.19 g of 4-acetonyloxy-5-nitrobenzofuran having a melting point of 78°C. Elemental analysis value C
Theoretical value C56 as llH9NO5. l7, H3.8C
) SN5.96 Experimental value C55.9F3sH3.69sN
6. 1.6y of the above compound O4 was dissolved in 50 mt of ethanol, 2 ml of Raney nickel was added, and catalytic reduction was carried out at normal pressure.
触媒を濾去し、溶媒を留去する。残渣にエトキシメチレ
ンマロン酸ジエチル１．６ｙを加えて１２０〜１３０゜
Ｃに４紛加熱する。これにポリリン酸エチル２５ｙを加
えて１３０〜１４０℃に１時間攪拌する。冷後、氷水を
加えて均一とし、析出晶を濾取し、エタノールより再結
晶すれば、融点２３５〜２３７℃の２・３−ジヒドロー
３−メチルー７−オキソー７Ｈ−フロ〔２・３−ｇ〕〔
１・４〕オキサジノ〔２・３・４−１−ｊ〕キノリンー
６−カルボン酸エチル１．３Ｖが得られる。元素分析値
Ｃｌ７Ｈｌ５ＮＯ．として
理論値Ｃ６５．ｌ７、Ｈ４．８次Ｎ４．４７実験値Ｃ６
５．４Ｏ．Ｈ４．８＆Ｎ４．５３上記化合物８００ｍｇ
、エタノール８ｍ１および５％水酸化ナトリウム水溶液
１６ｍ１の混合物を１００℃で１時間加熱する。The catalyst is filtered off and the solvent is distilled off. Add 1.6 y of diethyl ethoxymethylenemalonate to the residue and heat the mixture to 120-130°C. Ethyl polyphosphate 25y was added to this and stirred at 130-140°C for 1 hour. After cooling, add ice water to make it homogeneous, collect the precipitated crystals by filtration, and recrystallize from ethanol to obtain 2,3-dihydro-3-methyl-7-oxo7H-furo [2,3-g] with a melting point of 235-237°C. ] [
1.3V of ethyl 1.4]oxazino[2.3.4-1-j]quinoline-6-carboxylate is obtained. Elemental analysis value Cl7Hl5NO. The theoretical value C65. l7, H4.8 order N4.47 experimental value C6
5.4O. H4.8&N4.53 800mg of the above compound
, 8 ml of ethanol and 16 ml of 5% aqueous sodium hydroxide solution is heated at 100° C. for 1 hour.
エタノールを留去し、塩酸々性として析出晶を濾取し、
ジメチルホルムアミドとエタノールの混液より再結晶す
れば、融点〉３００℃の２●３−ジヒドロー３−メチル
ー７−オキソー７Ｈ−フロ〔２・３−ｇ〕〔１・４〕オ
キサジノ〔２・３・４−１，．ｊ〕キノリンー６−カル
ボン酸５３０ｍ９が得られる。元素分析値Ｃｌ５Ｈｌｌ
ＮＯ，として
理論値Ｃ６３．ｌ伝Ｈ３．９＆Ｎ４．９ｌ実験値Ｃ６２
．９表Ｈ４．ＯＯ、Ｎ５．Ｏ７実施例２２●３−ジヒド
ロー３−メチルー７−オキソー７Ｈ−フロ〔２・３−ｇ
〕〔１・４〕オキサジノ〔２・３・４−１−ｊ〕キノリ
ンー６−カルボン酸エチル１．０ｙをメタノール６０ｍ
ｔ１氷酢酸５ｍ１に加え、１０％のパラジウム炭８００
ｍ９で常圧接触還元する。Ethanol was distilled off, and the precipitated crystals were collected by filtration as hydrochloric acid.
Recrystallization from a mixture of dimethylformamide and ethanol yields 2●3-dihydro3-methyl-7-oxo7H-furo[2.3-g][1.4]oxazino[2.3.4] with a melting point of >300°C. -1,. j] 530 m9 of quinoline-6-carboxylic acid are obtained. Elemental analysis value Cl5Hll
NO, the theoretical value C63. lden H3.9&N4.9l experimental value C62
．． 9 Table H4. OO, N5. O7 Example 22 ● 3-dihydro 3-methyl-7-oxo 7H-furo [2.3-g
] [1.4] Oxazino[2.3.4-1-j] 1.0y of ethyl quinoline-6-carboxylate in 60m of methanol
t1 glacial acetic acid 5ml plus 10% palladium charcoal 800ml
Atmospheric pressure catalytic reduction is carried out using m9.
触媒を濾去し、濾縮して析出晶０．７ｙを濾取し、エタ
ノールから再結晶すれば、融点２４３〜２４５℃の２・
３・１０・１１−、テトララヒドロー３−メチルー７−
オキソー７Ｈ−フロ〔２●３−ｇ〕〔１・４〕オキサジ
ノ〔２・３・４−１ｊ〕キノリンー６−カルボン酸エチ
ルが得られる。元素分析値Ｃｌ７Ｈｌ７ＮＯ，として
理論値Ｃ６４．７＼Ｈ５．４４、Ｎ４．４４実験値Ｃ６
４．６ヌＨ５．５＼Ｎ４．２７上記化合物３６０ｍｇ、
エタノール４ｍ１および５％水酸化ナトリウム水溶液８
ｍＬの混合物を１００℃に１時間加熱する。If the catalyst is removed by filtration, 0.7y of precipitated crystals are collected by filtration, and recrystallized from ethanol, 2.
3,10,11-, tetrahydro-3-methyl-7-
Ethyl oxo7H-furo[2●3-g][1.4]oxazino[2.3.4-1j]quinoline-6-carboxylate is obtained. Elemental analysis value Cl7Hl7NO, theoretical value C64.7\H5.44, N4.44 experimental value C6
4.6 Nu H5.5\N4.27 360 mg of the above compound,
4 ml of ethanol and 8 ml of 5% aqueous sodium hydroxide solution
Heat mL of the mixture to 100° C. for 1 hour.
冷後、塩酸々性として析出晶を濾取し、クロロホルム−
エタノールから再結晶すれば、融点〉３００ムＣの２●
３●１０●１１−テトラヒドロー３−メチルー７−オキ
ソー７Ｈ−フロ〔２・３−ｇ〕〔１・４〕オキサジノ〔
２・３・４一ｉ−ｊ〕キノリンー６−カルボン酸２９３
ｍ９が得られる。元素分析値Ｃｌ５Ｈｌ３ＮＯ，としてAfter cooling, the precipitated crystals were collected by filtration as hydrochloric acid, and chloroform-
If recrystallized from ethanol, 2● with a melting point of >300 μC
3●10●11-Tetrahydro 3-methyl-7-oxo 7H-furo [2.3-g] [1.4] Oxazino [
2.3.41i-j]Quinoline-6-carboxylic acid 293
m9 is obtained. As elemental analysis value Cl5Hl3NO,
Claims (1)
０・１１−テトラヒドロフロ〔２・３−ｇ〕〔１・４〕
オキサジノ〔２・３・４−ｉ・ｊ〕キノリン誘導体また
はその塩。２ ２・３−ジヒドロ−３−メチル−７−オ
キソ−７Ｈ−フロ〔２・３−ｇ〕〔１・４〕オキサジノ
〔２・３・４−ｉ・ｊ〕キノリン−６−カルボン酸また
はその塩である特許請求の範囲第１項記載の化合物。 ３ ２・３・１０・１１−テトラヒドロ−３−メチル−
７−オキソ−７Ｈ−フロ〔２・３−ｇ〕〔１・４〕オキ
サジノ〔２・３・４−ｉ・ｊ〕キノリン−６−カルボン
酸またはその塩である特許請求の範囲第１項記載の化合
物。[Claims] 1 2,3-dihydrofuro or 2,3,1 represented by the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 represents a lower alkyl group.)
0,11-tetrahydrofuro [2,3-g] [1,4]
Oxazino[2,3,4-i,j]quinoline derivative or salt thereof. 2 2,3-dihydro-3-methyl-7-oxo-7H-furo[2,3-g][1,4]oxazino[2,3,4-i/j]quinoline-6-carboxylic acid or its The compound according to claim 1, which is a salt. 3 2,3,10,11-tetrahydro-3-methyl-
Claim 1, which is 7-oxo-7H-furo[2,3-g][1,4]oxazino[2,3,4-i,j]quinoline-6-carboxylic acid or a salt thereof compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7060878A JPS6042797B2 (en) | 1978-06-12 | 1978-06-12 | Furoquinoline derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7060878A JPS6042797B2 (en) | 1978-06-12 | 1978-06-12 | Furoquinoline derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS54163597A JPS54163597A (en) | 1979-12-26 |
| JPS6042797B2 true JPS6042797B2 (en) | 1985-09-25 |
Family
ID=13436462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7060878A Expired JPS6042797B2 (en) | 1978-06-12 | 1978-06-12 | Furoquinoline derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6042797B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS616683A (en) * | 1984-06-20 | 1986-01-13 | 富士通株式会社 | Crt display |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10237819A1 (en) | 2002-08-19 | 2004-03-04 | Bayer Ag | 5-Nitrobenzofurane |
-
1978
- 1978-06-12 JP JP7060878A patent/JPS6042797B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS616683A (en) * | 1984-06-20 | 1986-01-13 | 富士通株式会社 | Crt display |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS54163597A (en) | 1979-12-26 |
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