JPS6237638B2 - - Google Patents
Info
- Publication number
- JPS6237638B2 JPS6237638B2 JP7117878A JP7117878A JPS6237638B2 JP S6237638 B2 JPS6237638 B2 JP S6237638B2 JP 7117878 A JP7117878 A JP 7117878A JP 7117878 A JP7117878 A JP 7117878A JP S6237638 B2 JPS6237638 B2 JP S6237638B2
- Authority
- JP
- Japan
- Prior art keywords
- quinoline
- pyrido
- add
- furo
- oxo
- 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
- 150000001875 compounds Chemical class 0.000 claims description 29
- -1 alkaline earth metal salt Chemical class 0.000 claims description 17
- VXGYRCVTBHVXMZ-UHFFFAOYSA-N quinoline-6-carboxylic acid Chemical class N1=CC=CC2=CC(C(=O)O)=CC=C21 VXGYRCVTBHVXMZ-UHFFFAOYSA-N 0.000 claims description 14
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 8
- 150000001340 alkali metals Chemical class 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 238000000921 elemental analysis Methods 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000013078 crystal Substances 0.000 description 15
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
- 235000011167 hydrochloric acid Nutrition 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- SVHHAAQTOHCWJX-UHFFFAOYSA-N ethyl quinoline-6-carboxylate Chemical compound N1=CC=CC2=CC(C(=O)OCC)=CC=C21 SVHHAAQTOHCWJX-UHFFFAOYSA-N 0.000 description 5
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
- 229920000388 Polyphosphate Polymers 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 239000001205 polyphosphate Substances 0.000 description 3
- 235000011176 polyphosphates Nutrition 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- GMOLCSICTCPZCU-UHFFFAOYSA-N 1-benzofuran-5-amine Chemical compound NC1=CC=C2OC=CC2=C1 GMOLCSICTCPZCU-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000010446 mirabilite Substances 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- VJYJBBMMLIDJEF-UHFFFAOYSA-N 1-benzothiophen-2-amine Chemical compound C1=CC=C2SC(N)=CC2=C1 VJYJBBMMLIDJEF-UHFFFAOYSA-N 0.000 description 1
- ZUPYTANKWDPRDP-UHFFFAOYSA-N 1-benzothiophen-5-amine Chemical compound NC1=CC=C2SC=CC2=C1 ZUPYTANKWDPRDP-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- YYFLDZZDOUDZQM-UHFFFAOYSA-N 3-[1-[[4-(3-phenylquinolin-2-yl)phenyl]methyl]piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC2=CC=CC=C2C=C1C1=CC=CC=C1 YYFLDZZDOUDZQM-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- ZFDIRQKJPRINOQ-HWKANZROSA-N Ethyl crotonate Chemical compound CCOC(=O)\C=C\C ZFDIRQKJPRINOQ-HWKANZROSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003638 chemical reducing agent 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
- 238000003113 dilution method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 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
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は式
（式中ＹはＯまたはＳを、Ｚは−CH2−または
−CO−を、R1は水素または低級アルキル基を意
味する。）で表わされる２，３−ジヒドロまたは
２，３，10，11−テトラヒドロ−７−オキソ−
1H，7H−フロまたはチエノ〔２，３−ｇ〕ピリ
ド〔３，２，１−ｉ，ｊ〕キノリン−６−カルボ
ン酸誘導体またはそのアルカリ金属もしくはアル
カリ土類金属塩に関するものである。
本発明の化合物の製造方法の例を反応式を示し
て説明する。
式中R1および水素または低級アルキル基をR3
およびR4はそれぞれ低級アルキル基を意味しＹ
はＯまたはＳを、Ｚは−CH2−または−CO−を
意味する。
すなわち、５−アミノベンゾフランまたは５−
アミノベンゾチオフエン（）とアクリル酸誘導
体（）を無溶媒下またはエタノール、酢酸、ジ
メチルホルムアミド等の極性溶媒中室温乃至還流
温度で縮合させて化合物（）を製し、これをポ
リリン酸またはポリリン酸エステル類中80゜乃至
200℃に加熱するか、あるいはR2が水素の場合は
ｐ−トルエンスルホン酸クロリド等によりアミノ
基を保護したのち、塩化チオニル、五塩化燐等の
ハロゲン化剤を作用させて酸ハロゲニドへ誘導
し、ついでフリーデルクラフツ反応を行ない式
（）の化合物を製する。この化合物にアルコキ
シメチレンマロン酸エステル（）を反応させる
か、またはそのオキソ基をジエチルエーテル、テ
トラヒドロフラン等の非極性溶媒中水素化リチウ
ムアルミニウム等の水素化金属還元剤を作用させ
ることにより還元した化合物にアルコキシメチレ
ンマロン酸エステル（）を反応させると式
（）の化合物のＺがＣ＝Ｏであるもの、または
CH2であるものがそれぞれ得られる。反応は無溶
媒またはエタノール等の極性溶媒中50゜乃至150
℃に加熱して行なうのが適当である。これをポリ
リン酸またはポリリン酸エステル類中80゜乃至
200℃に加熱することにより閉環させて２，３−
ジヒドロ−７−オキソ−1H，7H−フロまたはチ
エノ〔２，３−ｇ〕ピリド〔３，２，１−ｉ，
ｊ〕キノリン−６−カルボン酸エステル誘導体
（）となし、これを酸または塩基で加水分解す
ると目的物（Ia）が得られる。また上記の化合物
（）をメタノール、エタノール等の極性溶媒中
パラジウム炭等の金属を触媒として接触還元して
２，３，10，11−テトラヒドロ体（）を製し、
これを上記と同様に加水分解するとテトラヒドロ
体の目的物（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す有用な化合
物である。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（MIC，μｇ／ml）
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 106／ml
培養条件 37℃、18時間
The present invention is based on the formula 2,3 -dihydro or 2,3,10, 11-tetrahydro-7-oxo-
It relates to 1H,7H-furo or thieno[2,3-g]pyrido[3,2,1-i,j]quinoline-6-carboxylic acid derivatives or their alkali metal or alkaline earth metal salts. An example of the method for producing the compound of the present invention will be explained by showing a reaction formula. In the formula, R 1 and hydrogen or lower alkyl group are replaced by R 3
and R 4 each mean a lower alkyl group, and Y
represents O or S, and Z represents -CH2- or -CO-. i.e. 5-aminobenzofuran or 5-
A compound () is prepared by condensing aminobenzothiophene () and an acrylic acid derivative () without a solvent or in a polar solvent such as ethanol, acetic acid, or dimethylformamide at room temperature to reflux temperature, and this is converted into polyphosphoric acid or polyphosphoric acid. 80° to esters
After heating to 200℃, or if R 2 is hydrogen, protect the amino group with p-toluenesulfonic acid chloride, etc., and then induce it to an acid halide by reacting with a halogenating agent such as thionyl chloride or phosphorus pentachloride. Then, a Friedel-Crafts reaction is performed to produce a compound of formula (). A compound obtained by reacting this compound with an alkoxymethylene malonic acid ester () or reducing its oxo group with a metal hydride reducing agent such as lithium aluminum hydride in a nonpolar solvent such as diethyl ether or tetrahydrofuran is obtained. When reacted with alkoxymethylene malonic acid ester (), Z of the compound of formula () is C=O, or
CH 2 is obtained respectively. The reaction is carried out without solvent or in a polar solvent such as ethanol at a temperature of 50° to 150°.
It is appropriate to carry out heating to ℃. 80° to 80° in polyphosphoric acid or polyphosphoric esters.
By heating to 200℃, the ring is closed and 2,3-
dihydro-7-oxo-1H,7H-furo or thieno[2,3-g]pyrido[3,2,1-i,
j] A quinoline-6-carboxylic acid ester derivative (), which is hydrolyzed with an acid or a base to obtain the target compound (Ia). Further, the above compound () is catalytically reduced in a polar solvent such as methanol or ethanol using a metal such as palladium charcoal as a catalyst to produce a 2,3,10,11-tetrahydro compound (),
This is hydrolyzed in the same manner as above to obtain the tetrahydro 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 compounds of the present invention are useful compounds that exhibit excellent antibacterial activity against Gram-negative and Gram-positive bacteria. Next, in vitro antibacterial test data and synthetic experiment examples are shown. Minimum inhibitory concentration (MIC, μg/ml) Japanese Society of Chemotherapy Standard method: Plate dilution method (heart infusion agar medium) Inoculum amount 10 6 /ml Culture conditions 37℃, 18 hours
【表】
実施例 １
５−アミノベンゾフラン10.0ｇおよびアクリル
酸メチル6.8ｇに酢酸0.1mlを加えて20時間還流す
る。減圧下に溶媒を留去し、残渣にｐ−トルエン
スルホン酸クロリド17ｇおよびピリジン100mlを
加えて80〜90℃に１時間加熱する。冷後水200ml
を加え、エーテルで生成物を抽出する。抽出液は
稀塩酸、稀水酸化カリ、水の順序で洗い、芒硝で
乾燥したのちエーテルを留去する。残渣を80％含
水メタノール100mlにとかし、室温で10％水酸化
カリ40mlを滴下する。更に１時間撹拌し、水200
mlを加えて塩酸で中和したのちクロロホルムで抽
出する。抽出液よりＮ−（５−ベンゾフリル）−Ｎ
−（ｐ−トルエンスルホニル）−β−アラニン4.8
ｇを得る。融点129〜130℃。
元素分析値 C18H17NO5Sとして
理論値 C60.15、H4.76、N3.89
実験値 C59.84、H4.82、N3.92
上記化合物5.4ｇをベンゼン30mlにとかし氷冷
下に五塩化燐３ｇを加える。徐々に加熱し100℃
で30分撹拌する。冷却し、塩化アルミニウム2.5
ｇを加えて室温で３時間撹拌する。10％塩酸50ml
を加えてベンゼン層を分離し水層はクロロホルム
で抽出する。有機溶媒を合せて水洗し、乾燥した
のち溶媒を留去する。残渣をクロロホルムにとか
してシリカゲルクロマトで分離精製し、クロロホ
ルム溶出分より６，７，８，９−テトラヒドロ−
９−オキソフロ〔３，２−ｆ〕キノリン1.5ｇ
（Ｖ，Ｙ＝Ｓ，R1＝Ｈ）を得る。融点130〜134
℃、無色針状晶。
元素分析値 C11H9NO2として
理論値 C70.57、H4.84、N7.47
実験値 C70.54、H4.87、N7.38
上記化合物0.5ｇをエトキシメチレンマロン酸
ジエチル0.6ｇに加え、130〜150℃に２時間加熱
する。冷後固型物をエーテルで処理し濾取する。
エタノールより再結晶すれば無色針状晶として融
点98〜99℃の６−〔２，２−ビス（エトキシカル
ボニル）エテニル〕−６，７，８，９−テトラヒ
ドロ−９−オキソフロ〔３，２−ｆ〕キノリン
0.72ｇが得られる。
元素分析値 C19H19NO6として
理論値 C63.86、H5.35、N3.91
実験値 C63.64、H5.42、N3.90
上記化合物2.5ｇをポリリン酸エチル20ｇに加
え、120℃に20分間加熱する。冷後水100mlを加え
て析出晶を濾取し、エタノールから再結晶して淡
黄色プリズム晶として融点276〜278℃の２，３−
ジヒドロ−１，７−ジオキソ−1H，7H−フロ
〔２，３−ｇ〕ピリド〔３，２，１−ｉ，ｊ〕キ
ノリン−６−カルボン酸エチル1.3ｇを得る。
元素分析値 C17H13NO5として
理論値 C65.59、H4.20、N4.49
実験値 C65.46、H4.34、N4.48
上記化合物0.8ｇを1N塩酸−90％酢酸10mlに加
え、120℃に２時間加熱する。析出晶を濾取し、
ジメチルホルムアミドから再結晶して淡黄色針状
晶として融点300℃以上の１，２，３−トリヒド
ロ−１，６−ジオキソ−6H−フロ〔２，３−
ｇ〕ピリド〔３，２，１−ｉ，ｊ〕キノリン−５
−カルボン酸0.4ｇを得る。
元素分析値 C15H9NO5として
理論値 C63.60、H3.20、N4.94
実験値 C63.52、H3.52、N5.15
実施例 ２
６，７，８，９−テトラヒドロ−９−オキソフ
ロ〔３，２−ｆ〕キノリン1.0ｇをエーテル100ml
にとかし、水素化リチウムアルミニウム0.4ｇを
加えて１時間還流する。水を加えてエーテル層を
分離し、芒硝で乾燥したのち、エーテルを留去す
る。残渣をクロロホルムにとかし、シリカゲルク
ロマトで分離精製し、クロロホルム溶出分より油
状の６，７，８，９−テトラヒドロフロ〔３，２
−ｆ〕キノリン0.8ｇを得る。これにエトキシメ
チレンマロン酸ジエチル1.1ｇを加えて120〜125
℃に1.5時間加熱する。放冷後、エーテルを加え
て不溶分を濾取し、石油エーテルより再結晶して
無色板状晶として融点83〜84℃の６−〔２，２−
ビス（エトキシカルボニル）−エテニル〕−６，
７，８，９−テトラヒドロ〔３，２−ｆ〕キノリ
ン1.0ｇを得る。
元素分析値 C19H21NO5として
理論値 C66.45、H6.16、N4.07
実験値 C66.44、H6.19、N4.14
上記化合物5.0ｇにポリリン酸エチル45ｇを加
え、120℃に20分間加熱する。冷後、水を加えて
クロロホルムで生成物を抽出する。抽出物をエタ
ノールから再結晶して無色針状晶として融転256
〜259℃の２，３−ジヒドロ−７−オキソ−1H，
7H−フロ〔２，３−ｇ〕ピリド〔３，２，１−
ｉ，ｊ〕キノリン−６−カルボン酸エチル3.4ｇ
を得る。
元素分析値 C17H15NO4として
理論値 C68.67、H5.08、N4.70
実験値 C68.57、H5.21、N5.19
上記化合物0.8ｇを10％水酸化ナトリウム液50
mlに加え、100℃で１時間加熱する。放冷後、塩
酸々性として析出晶を濾取し、ジメチルホルムア
ミドから再結晶して無色針状晶として融点300℃
以上の２，３−ジヒドロ−７−オキソ−1H，7H
−フロ〔２，３−ｇ〕ピリド〔３，２，１−ｉ，
ｊ〕キノリン−６−カルボン酸0.3ｇを得る。
元素分析値 C15H11NO4として
理論値 C66.91、H4.11、N5.20
実験値 C66.65、H4.26、N5.39
実施例 ３
実施例１で用いたアクリル酸メチルの代りにク
ロトン酸エチルを用いて全く同様の反応を実施
し、次の中間体及び目的物を得た。
７−ムメチル−６，７，８，９−テトラヒドロ
−９−オキソフロ〔３，２−ｆ〕キノリン融点
108〜110℃
元素分析値 C12H11NO2として
理論値 C71.63、H5.50、N6.95
実験値 C71.42、H5.63、N6.79
２，３−ジヒドロ−３−メチル−７−オキソ−
1H，7H−フロ〔２，３−ｇ〕ピリド〔３，２，
１−ｉ，ｊ〕キノリン−６−カルボン酸エチル
融点260〜262℃（エタノールより再結晶無色針状
晶）
元素分析値 C18H17NO4として
理論値 C69.44、H5.50、N4.49
実験値 C69.78、H5.60、N4.64
２，３−ジヒドロ−３−メチル−７−オキソ−
1H，7H−フロ〔２，３−ｇ〕ピリド〔３，２，
１−ｉ，ｊ〕キノリン−６−カルボン酸
融点253〜255℃（エタノールより再結晶無色針状
晶）
元素分析値 C16H13NO4として
理論値 C67.84、H4.62、N4.94
実験値 C67.35、H4.95、N4.85
実施例 ４
２，３−ジヒドロ−７−オキソ−1H，7H−フ
ロ〔２，３−ｇ〕ピリド〔３，２，１−ｉ，ｊ〕
キノリン−６−カルボン酸エチル0.7ｇをメタノ
ール200mlにとかし、10％パラジウム炭0.2ｇを加
えて常温常圧下に接触還元を行う。パラジウム炭
を濾去してメタノールを留去し、残渣をエタノー
ルから再結晶して融点213〜214℃の無色針状晶と
して２，３，10，11−テトラヒドロ−７−オキソ
−1H，7H−フロ〔２，３−ｇ〕ピリド〔３，
２，１−ｉ，ｊ〕キノリン−６−カルボン酸エチ
ル0.5ｇを得る。
元素分析値 C17H17NO4として
理論値 C68.21、H5.72、N4.67
実験値 C68.19、H5.53、N4.62
上記化合物0.5ｇを10％水酸化ナトリウム液８
mlに加えて30分間還流する。冷後、塩酸々性と
し、析出晶を濾取してジメチルホルムアミドから
再結晶して融点300℃以上の無色針状晶として
２，３，10，11−テトラヒドロ−７−オキソ−
1H，7H−フロ〔２，３−ｇ〕ピリド〔３，２，
１−ｉ，ｊ〕キノリン−６−カルボン酸0.2ｇを
得る。
元素分析値 C15H13NO4として
理論値 C66.41、H4.82、N5.16
実験値 C66.36、H4.90、N5.25
実施例 ５
２，３−ジヒドロ−３−メチル−７−オキソ−
1H，7H−フロ〔２，３−ｇ〕ピリド〔３，２，
１−ｉ，ｊ〕キノリン−６−カルボン酸エチル
1.25ｇをメタノール200mlにとかし、10％パラジ
ウム炭0.3ｇを加えて常温常圧下に接触還元を行
う。触媒を濾去してメタノールを留去し、残渣を
エタノールから再結晶して融点214〜216℃の無色
針状晶として２，３，10，11−テトラヒドロ−３
−メチル−７−オキソ−1H，7H−フロ〔２，３
−ｇ〕ピリド〔３，２，１−ｉ，ｊ〕キノリン−
６−カルボン酸エチル0.88ｇを得る。
元素分析値 C18H19NO4として
理論値 C68.99、H6.11、N4.46
実験値 C69.21、H6.07、N4.57
上記化合物0.63ｇを10％水酸化ナトリウム液10
mlに加えて１時間還流する。冷後、塩酸々性と
し、析出晶を濾取してジメチルホルムアミドから
再結晶すると融点285〜290℃の無色針状晶として
２，３，10，11−テトラヒドロ−３−メチル−７
−オキソ−1H，7H−フロ〔２，３−ｇ〕ピリド
〔３，２，１−ｉ，ｊ〕キノリン−６−カルボン
酸0.32ｇを得る。
元素分析値 C16H15NO4として
理論値 C67.35、H5.30、N4.90
実験値 C67.10、H5.28、N4.91
実施例 ６
５−アミノベンゾチオフエン22.4ｇおよびアク
リル酸メチル13.0ｇに酢酸0.5mlを加えて15時間
還流する。エーテルを加えて水洗し無水炭酸カリ
で乾燥して溶媒を留去する。残渣にピリジン200
mlおよびｐ−トルエンスルホン酸クロリド32.5ｇ
を加えて30分間環流する。冷後、水を加えてエー
テルで抽出し、抽出液は10％塩酸、次いで水で洗
い、乾燥後、溶媒を留去する。残渣にメタノール
200mlおよび10％水酸化カリ80mlを加えて２時間
還流する。メタノールを留去し、塩酸々性として
エーテルで抽出する。抽出液は水洗し、乾燥した
のち、溶媒を留去する。残渣をベンゼンから再結
晶して融点82〜83℃のＮ−（５−ベンゾチエニ
ル）−Ｎ−（ｐ−トルエンスルホニル）−β−アラ
ニン39.5ｇを得る。
元素分析値 C18H17NO4S2として
理論値 C57.58、H4.57、N3.73
実験値 C57.32、H4.69、N3.54
上記化合物37.5ｇをベンゼン200mlに加え、五
塩化燐21ｇを少しづつ加え、30分間還流する。冷
却し、塩化第ニスズ18ml、ベンゼン80mlの溶媒を
滴下する。室温で５時間撹拌したのち、氷水にあ
け水層はエーテルで抽出する。有機溶媒層を合せ
て水洗し、乾燥したのち溶媒を留去する。残渣に
酢酸100ml、濃塩酸100mlおよび水40mlを加えて３
時間還流する。冷後、水を加えて20％水酸化カリ
でアルカリ性とし、エーテルで抽出する。抽出液
は水洗し、乾燥したのち溶媒を留去する。残渣を
エタノールから再結晶して融点141〜143℃の６，
７，８，９−テトラヒドロ−９−オキソチエノ
〔３，２−ｆ〕キノリン14.0ｇを得る。
元素分析値 C11H9NOSとして
理論値 C65.00、H4.46、N6.89
実験値 C65.12、H4.64、N6.71
上記化合物6.1ｇをテトラヒドロフラン160mlに
とかし、これに水素化リチウムアルミニウム2.3
ｇを加えて１時間還流する。水およびエーテルを
加えて有機溶媒層を分取し、水洗、乾燥したのち
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6.2ｇを加えて120℃に１時間加熱す
る。冷後、イソプロピルエーテルで処理し、６−
〔２，２−ビス（エトキシカルボニル）エテニ
ル〕−６，７，８，９−テトラヒドロチエフ
〔３，２−ｆ〕キノリン3.5ｇを得る。
上記化合物2.0ｇとポリリン酸エチル15ｇの混
合物を115〜125℃に30分間加熱する。冷後、氷水
を加えてクロロホルムで抽出する。抽出液は水洗
し、乾燥したのちクロロホルムを留去する。残渣
をエタノールから再結晶して融点208〜209℃の
２，３−ジヒドロ−７−オキソ−1H，7H−チエ
ノ〔２，３−ｇ〕ピリド〔３，２，１−ｉ，ｊ〕
キノリン−６−カルボン酸エチル1.3ｇを得る。
元素分析値 C17H15NO3Sとして
理論値 C65.15、H4.82、N4.47
実験値 C65.02、H4.86、N4.39
上記化合物1.1ｇを10％水酸化ナトリウム50ml
に加え、100℃で１時間加熱する。塩酸々性とし
て析出晶を濾取し、ジメチルホルムアミドから再
結晶して融点295〜298℃(d)の結晶として２，３−
ジヒドロ−７−オキソ−1H，7H−チエノ〔２，
３−ｇ〕ピリド〔３，２，１−ｉ，ｊ〕キノリン
−６−カルボン酸0.35ｇを得る。
元素分析値 C15H11NO3Sとして
理論値 C63.14、H3.89、N4.91
実験値 C62.98、H4.01、N4.86[Table] Example 1 0.1 ml of acetic acid was added to 10.0 g of 5-aminobenzofuran and 6.8 g of methyl acrylate, and the mixture was refluxed for 20 hours. The solvent is distilled off under reduced pressure, 17 g of p-toluenesulfonic acid chloride and 100 ml of pyridine are added to the residue, and the mixture is heated to 80-90°C for 1 hour. 200ml of cold water
and extract the product with ether. The extract was washed in the order of dilute hydrochloric acid, dilute potassium hydroxide, and water, dried over Glauber's salt, and then the ether was distilled off. Dissolve the residue in 100 ml of 80% aqueous methanol, and add 40 ml of 10% potassium hydroxide dropwise at room temperature. Stir for another hour and add 200 ml of water.
ml, neutralized with hydrochloric acid, and extracted with chloroform. N-(5-benzofuryl)-N from the extract
-(p-toluenesulfonyl)-β-alanine 4.8
get g. Melting point 129-130℃. Elemental analysis value C 18 H 17 NO 5 As S Theoretical value C60.15, H4.76, N3.89 Experimental value C59.84, H4.82, N3.92 Dissolve 5.4 g of the above compound in 30 ml of benzene and cool on ice. Add 3 g of phosphorus pentachloride. Gradually heat to 100℃
Stir for 30 minutes. Cooled aluminum chloride 2.5
g and stirred at room temperature for 3 hours. 10% hydrochloric acid 50ml
is added to separate the benzene layer, and the aqueous layer is extracted with chloroform. The organic solvents are combined, washed with water, dried, and then the solvent is distilled off. The residue was dissolved in chloroform, separated and purified using silica gel chromatography, and 6,7,8,9-tetrahydro-
9-oxofuro[3,2-f]quinoline 1.5g
(V, Y=S, R 1 =H) is obtained. Melting point 130-134
°C, colorless needles. Elemental analysis value C 11 H 9 NO 2 Theoretical value C70.57, H4.84, N7.47 Experimental value C70.54, H4.87, N7.38 Add 0.5 g of the above compound to 0.6 g of diethyl ethoxymethylenemalonate. , heat to 130-150°C for 2 hours. After cooling, the solid is treated with ether and filtered.
When recrystallized from ethanol, 6-[2,2-bis(ethoxycarbonyl)ethenyl]-6,7,8,9-tetrahydro-9-oxofuro[3,2- f] Quinoline
0.72g is obtained. Elemental analysis value C 19 H 19 NO 6 Theoretical value C63.86, H5.35, N3.91 Experimental value C63.64, H5.42, N3.90 Add 2.5 g of the above compound to 20 g of ethyl polyphosphate and heat at 120°C. Heat for 20 minutes. After cooling, add 100 ml of water, collect the precipitated crystals by filtration, and recrystallize from ethanol to obtain pale yellow prismatic crystals with a melting point of 276-278°C.
1.3 g of ethyl dihydro-1,7-dioxo-1H,7H-furo[2,3-g]pyrido[3,2,1-i,j]quinoline-6-carboxylate is obtained. Elemental analysis value C 17 H 13 NO 5 Theoretical value C65.59, H4.20, N4.49 Experimental value C65.46, H4.34, N4.48 Add 0.8 g of the above compound to 10 ml of 1N hydrochloric acid - 90% acetic acid. , heat to 120°C for 2 hours. Filter the precipitated crystals,
1,2,3-trihydro-1,6-dioxo-6H-furo[2,3-trihydro-1,6-dioxo-6H-furo[2,3-
g] Pyrido[3,2,1-i,j]quinoline-5
- 0.4 g of carboxylic acid is obtained. Elemental analysis value C 15 H 9 NO 5 Theoretical value C63.60, H3.20, N4.94 Experimental value C63.52, H3.52, N5.15 Example 2 6,7,8,9-tetrahydro-9 - Oxofuro [3,2-f] 1.0 g of quinoline in 100 ml of ether
Add 0.4 g of lithium aluminum hydride and reflux for 1 hour. Water was added to separate the ether layer, dried over Glauber's salt, and the ether was distilled off. The residue was dissolved in chloroform, separated and purified using silica gel chromatography, and the chloroform eluate was extracted as an oily 6,7,8,9-tetrahydrofuro[3,2
-f] Obtain 0.8 g of quinoline. Add 1.1g of diethyl ethoxymethylene malonate to this and make the mixture 120~125
Heat to ℃ for 1.5 hours. After cooling, ether was added, insoluble matter was filtered out, and recrystallized from petroleum ether to give colorless plate-like crystals of 6-[2,2-
bis(ethoxycarbonyl)-ethenyl]-6,
1.0 g of 7,8,9-tetrahydro[3,2-f]quinoline is obtained. Elemental analysis value C 19 H 21 NO 5 Theoretical value C66.45, H6.16, N4.07 Experimental value C66.44, H6.19, N4.14 Add 45 g of ethyl polyphosphate to 5.0 g of the above compound and heat to 120℃ Heat for 20 minutes. After cooling, add water and extract the product with chloroform. The extract was recrystallized from ethanol and melted as colorless needles256
2,3-dihydro-7-oxo-1H at ~259°C,
7H-Furo[2,3-g]pyrido[3,2,1-
i, j] Ethyl quinoline-6-carboxylate 3.4 g
get. Elemental analysis value C 17 H 15 NO 4 Theoretical value C68.67, H5.08, N4.70 Experimental value C68.57, H5.21, N5.19 Add 0.8 g of the above compound to 10% sodium hydroxide solution 50
ml and heat at 100℃ for 1 hour. After cooling, the precipitated crystals are collected by filtration as hydrochloric acids, and recrystallized from dimethylformamide to form colorless needle crystals with a melting point of 300°C.
2,3-dihydro-7-oxo-1H,7H
-Furo[2,3-g]pyrido[3,2,1-i,
j] Obtain 0.3 g of quinoline-6-carboxylic acid. Elemental analysis value C 15 H 11 NO 4 Theoretical value C66.91, H4.11, N5.20 Experimental value C66.65, H4.26, N5.39 Example 3 Substitute for methyl acrylate used in Example 1 Exactly the same reaction was carried out using ethyl crotonate to obtain the following intermediate and target product. 7-Methyl-6,7,8,9-tetrahydro-9-oxofuro[3,2-f]quinoline melting point
108-110℃ Elemental analysis value C 12 H 11 NO 2 Theoretical value C71.63, H5.50, N6.95 Experimental value C71.42, H5.63, N6.79 2,3-dihydro-3-methyl- 7-oxo-
1H,7H-furo[2,3-g]pyrido[3,2,
1-i,j] Ethyl quinoline-6-carboxylate Melting point 260-262℃ (colorless needle crystals recrystallized from ethanol) Elemental analysis value C 18 H 17 NO 4 Theoretical value C69.44, H5.50, N4. 49 Experimental values C69.78, H5.60, N4.64 2,3-dihydro-3-methyl-7-oxo-
1H,7H-furo[2,3-g]pyrido[3,2,
1-i,j]Quinoline-6-carboxylic acid Melting point 253-255℃ (colorless needle crystals recrystallized from ethanol) Elemental analysis value C 16 H 13 NO 4 Theoretical value C67.84, H4.62, N4.94 Experimental values C67.35, H4.95, N4.85 Example 4 2,3-dihydro-7-oxo-1H,7H-furo[2,3-g]pyrido[3,2,1-i,j]
Dissolve 0.7 g of ethyl quinoline-6-carboxylate in 200 ml of methanol, add 0.2 g of 10% palladium charcoal, and perform catalytic reduction at room temperature and pressure. The palladium charcoal was filtered off, methanol was distilled off, and the residue was recrystallized from ethanol to give 2,3,10,11-tetrahydro-7-oxo-1H,7H- as colorless needle crystals with a melting point of 213-214°C. Furo[2,3-g]pyrido[3,
0.5 g of ethyl 2,1-i,j]quinoline-6-carboxylate is obtained. Elemental analysis value C 17 H 17 NO 4 Theoretical value C68.21, H5.72, N4.67 Experimental value C68.19, H5.53, N4.62 Add 0.5 g of the above compound to 10% sodium hydroxide solution 8
ml and reflux for 30 minutes. After cooling, the precipitated crystals were acidified with hydrochloric acid, and the precipitated crystals were collected by filtration and recrystallized from dimethylformamide to give 2,3,10,11-tetrahydro-7-oxo-
1H,7H-furo[2,3-g]pyrido[3,2,
1-i,j] 0.2 g of quinoline-6-carboxylic acid is obtained. Elemental analysis value C 15 H 13 NO 4 Theoretical value C66.41, H4.82, N5.16 Experimental value C66.36, H4.90, N5.25 Example 5 2,3-dihydro-3-methyl-7 -Oxo-
1H,7H-furo[2,3-g]pyrido[3,2,
1-i,j] Ethyl quinoline-6-carboxylate
Dissolve 1.25 g in 200 ml of methanol, add 0.3 g of 10% palladium on charcoal, and perform catalytic reduction at room temperature and pressure. The catalyst was filtered off, methanol was distilled off, and the residue was recrystallized from ethanol to give 2,3,10,11-tetrahydro-3 as colorless needles with a melting point of 214-216°C.
-Methyl-7-oxo-1H,7H-furo[2,3
-g]pyrido[3,2,1-i,j]quinoline-
0.88 g of ethyl 6-carboxylate is obtained. Elemental analysis value C 18 H 19 NO 4 Theoretical value C68.99, H6.11, N4.46 Experimental value C69.21, H6.07, N4.57 Add 0.63g of the above compound to 10% sodium hydroxide solution 10
ml and reflux for 1 hour. After cooling, the precipitated crystals are acidified with hydrochloric acid, and the precipitated crystals are filtered and recrystallized from dimethylformamide to give 2,3,10,11-tetrahydro-3-methyl-7 as colorless needle crystals with a melting point of 285-290°C.
0.32 g of -oxo-1H,7H-furo[2,3-g]pyrido[3,2,1-i,j]quinoline-6-carboxylic acid is obtained. Elemental analysis value C 16 H 15 NO 4 Theoretical value C67.35, H5.30, N4.90 Experimental value C67.10, H5.28, N4.91 Example 6 22.4 g of 5-aminobenzothiophene and acrylic acid Add 0.5 ml of acetic acid to 13.0 g of methyl and reflux for 15 hours. Add ether, wash with water, dry over anhydrous potassium carbonate, and distill off the solvent. Pyridine 200 on the residue
ml and p-toluenesulfonic acid chloride 32.5g
Add and reflux for 30 minutes. After cooling, water is added and extracted with ether. The extract is washed with 10% hydrochloric acid and then with water. After drying, the solvent is distilled off. methanol to the residue
Add 200 ml and 80 ml of 10% potassium hydroxide and reflux for 2 hours. Methanol is distilled off, and the mixture is diluted with hydrochloric acid and extracted with ether. The extract is washed with water, dried, and then the solvent is distilled off. The residue is recrystallized from benzene to obtain 39.5 g of N-(5-benzothienyl)-N-(p-toluenesulfonyl)-β-alanine having a melting point of 82-83°C. Elemental analysis value C 18 H 17 NO 4 S 2 Theoretical value C57.58, H4.57, N3.73 Experimental value C57.32, H4.69, N3.54 Add 37.5 g of the above compound to 200 ml of benzene and convert into pentachloride. Add 21 g of phosphorus little by little and reflux for 30 minutes. After cooling, a solvent of 18 ml of stannous chloride and 80 ml of benzene was added dropwise. After stirring at room temperature for 5 hours, the mixture was poured into ice water and the aqueous layer was extracted with ether. The organic solvent layers are combined, washed with water, dried, and then the solvent is distilled off. Add 100 ml of acetic acid, 100 ml of concentrated hydrochloric acid and 40 ml of water to the residue.
Reflux for an hour. After cooling, add water, make alkaline with 20% potassium hydroxide, and extract with ether. The extract is washed with water, dried, and then the solvent is distilled off. The residue was recrystallized from ethanol to give 6, with a melting point of 141-143℃.
14.0 g of 7,8,9-tetrahydro-9-oxothieno[3,2-f]quinoline are obtained. Elemental analysis value C 11 H 9 As NOS Theoretical value C65.00, H4.46, N6.89 Experimental value C65.12, H4.64, N6.71 Dissolve 6.1 g of the above compound in 160 ml of tetrahydrofuran, and add lithium hydride to this. aluminum 2.3
g and reflux for 1 hour. Water and ether are added to separate the organic solvent layer, washed with water, dried, and then the solvent is distilled off. Add 6.2 g of diethyl ethoxymethylenemalonate to the residue and heat at 120°C for 1 hour. After cooling, treatment with isopropyl ether and 6-
3.5 g of [2,2-bis(ethoxycarbonyl)ethenyl]-6,7,8,9-tetrahydrothief[3,2-f]quinoline are obtained. A mixture of 2.0 g of the above compound and 15 g of ethyl polyphosphate is heated to 115-125°C for 30 minutes. After cooling, add ice water and extract with chloroform. The extract is washed with water, dried, and then the chloroform is distilled off. The residue was recrystallized from ethanol to give 2,3-dihydro-7-oxo-1H,7H-thieno[2,3-g]pyrid[3,2,1-i,j] with a melting point of 208-209°C.
1.3 g of ethyl quinoline-6-carboxylate is obtained. Elemental analysis value C 17 H 15 NO 3 As S Theoretical value C65.15, H4.82, N4.47 Experimental value C65.02, H4.86, N4.39 Add 1.1 g of the above compound to 50 ml of 10% sodium hydroxide
and heat at 100℃ for 1 hour. The precipitated crystals were collected by filtration as hydrochloric acid, and recrystallized from dimethylformamide to give 2,3-
Dihydro-7-oxo-1H,7H-thieno[2,
0.35 g of 3-g]pyrido[3,2,1-i,j]quinoline-6-carboxylic acid is obtained. Elemental analysis value C 15 H 11 NO 3 S Theoretical value C63.14, H3.89, N4.91 Experimental value C62.98, H4.01, N4.86
Claims (1)
−CO−を、R1は水素または低級アルキル基を示
す。）で表わされる２，３−ジヒドロまたは２，
３，10，11−テトラヒドロ−７−オキソ−1H，
7H−フロまたはチエノ〔２，３−ｇ〕ピリド
〔３，２，１−ｉ，ｊ〕キノリン−６−カルボン
酸誘導体またはその塩。 ２ ２，３−ジヒドロ−７−オキソ−1H，7H−
フロ〔２，３−ｇ〕ピリド〔３，２，１−ｉ，
ｊ〕キノリン−６−カルボン酸またはそのアルカ
リ金属もしくはアルカリ土類金属塩である特許請
求の範囲第１項の化合物。 ３ ２，３−ジヒドロ−３−メチル−７−オキソ
−1H，7H−フロ〔２，３−ｇ〕ピリド〔３，
２，１−ｉ，ｊ〕キノリン−６−カルボン酸また
はそのアルカリ金属もしくはアルカリ土類金属塩
である特許請求の範囲第１項の化合物。 ４ ２，３−ジヒドロ−１，７−ジオキソ−
1H，7H−フロ〔２，３−ｇ〕ピリド〔３，２，
１−ｉ，ｊ〕キノリン−６−カルボン酸またはそ
のアルカリ金属もしくはアルカリ土類金属塩であ
る特許請求の範囲第１項の化合物。 ５ ２，３，10，11−テトラヒドロ−７−オキソ
−1H，7H−フロ〔２，３−ｇ〕ピリド〔３，
２，１−ｉ，ｊ〕キノリン−６−カルボン酸また
はそのアルカリ金属もしくはアルカリ土類金属塩
である特許請求の範囲第１項の化合物。 ６ ２，３，10，11−テトラヒドロ−３−メチル
−７−オキソ−1H，7H−フロ〔２，３−ｇ〕ピ
リド〔３，２，１−ｉ，ｊ〕キノリン−６−カル
ボン酸またはそのアルカリ金属もしくはアルカリ
土類金属塩である特許請求の範囲第１項の化合
物。 ７ ２，３−ジヒドロ−７−オキソ−1H，7H−
チエノ〔２，３−ｇ〕ピリド〔３，２，１−ｉ，
ｊ〕キノリン−６−カルボン酸またはそのアルカ
リ金属もしくはアルカリ土類金属塩である特許請
求の範囲第１項の化合物。[Claims] 1 formula 2,3 - dihydro or 2 ,
3,10,11-tetrahydro-7-oxo-1H,
7H-furo or thieno[2,3-g]pyrido[3,2,1-i,j]quinoline-6-carboxylic acid derivative or salt thereof. 2 2,3-dihydro-7-oxo-1H,7H-
Furo[2,3-g]pyrido[3,2,1-i,
j] The compound according to claim 1, which is quinoline-6-carboxylic acid or an alkali metal or alkaline earth metal salt thereof. 3 2,3-dihydro-3-methyl-7-oxo-1H,7H-furo[2,3-g]pyrido[3,
2,1-i,j]quinoline-6-carboxylic acid or an alkali metal or alkaline earth metal salt thereof. 4 2,3-dihydro-1,7-dioxo-
1H,7H-furo[2,3-g]pyrido[3,2,
1-i,j] The compound according to claim 1, which is quinoline-6-carboxylic acid or an alkali metal or alkaline earth metal salt thereof. 5 2,3,10,11-tetrahydro-7-oxo-1H,7H-furo[2,3-g]pyrido[3,
2,1-i,j]quinoline-6-carboxylic acid or an alkali metal or alkaline earth metal salt thereof. 6 2,3,10,11-tetrahydro-3-methyl-7-oxo-1H,7H-furo[2,3-g]pyrido[3,2,1-i,j]quinoline-6-carboxylic acid or The compound according to claim 1, which is an alkali metal or alkaline earth metal salt thereof. 7 2,3-dihydro-7-oxo-1H,7H-
Thieno[2,3-g]pyrido[3,2,1-i,
j] The compound according to claim 1, which is quinoline-6-carboxylic acid or an alkali metal or alkaline earth metal salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7117878A JPS54163598A (en) | 1978-06-13 | 1978-06-13 | Pyridoquinoline derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7117878A JPS54163598A (en) | 1978-06-13 | 1978-06-13 | Pyridoquinoline derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS54163598A JPS54163598A (en) | 1979-12-26 |
| JPS6237638B2 true JPS6237638B2 (en) | 1987-08-13 |
Family
ID=13453137
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7117878A Granted JPS54163598A (en) | 1978-06-13 | 1978-06-13 | Pyridoquinoline derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS54163598A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7008940B1 (en) | 1999-08-20 | 2006-03-07 | Takeda Pharmaceutical Company Limited | Dihydrobenzofuran derivatives, process for the preparing thereof and agents |
-
1978
- 1978-06-13 JP JP7117878A patent/JPS54163598A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS54163598A (en) | 1979-12-26 |
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