JPH0317838B2 - - Google Patents
Info
- Publication number
- JPH0317838B2 JPH0317838B2 JP20544189A JP20544189A JPH0317838B2 JP H0317838 B2 JPH0317838 B2 JP H0317838B2 JP 20544189 A JP20544189 A JP 20544189A JP 20544189 A JP20544189 A JP 20544189A JP H0317838 B2 JPH0317838 B2 JP H0317838B2
- Authority
- JP
- Japan
- Prior art keywords
- chloroform
- residue
- added
- mixture
- water
- 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
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 150000001875 compounds Chemical class 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 6
- -1 2,3-difluoro-6-nitrophenyl oxiranylmethyl ether Chemical compound 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000010446 mirabilite Substances 0.000 description 4
- 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 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- HRUQKPXEKXZHBS-UHFFFAOYSA-N 1-(2,3-difluoro-6-nitrophenoxy)-3-methoxypropan-2-one Chemical compound COCC(=O)COC1=C(F)C(F)=CC=C1[N+]([O-])=O HRUQKPXEKXZHBS-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- KEGOHDCHURMFKX-UHFFFAOYSA-N 2,3-difluoro-6-nitrophenol Chemical compound OC1=C(F)C(F)=CC=C1[N+]([O-])=O KEGOHDCHURMFKX-UHFFFAOYSA-N 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- SNTZGENQEQKPHV-UHFFFAOYSA-N O1CC=NC2=CC(C(=O)OCC)=CC=C21 Chemical compound O1CC=NC2=CC(C(=O)OCC)=CC=C21 SNTZGENQEQKPHV-UHFFFAOYSA-N 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 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
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
【発明の詳細な説明】
本発明は一般式
（式中R1は低級アルキル基を意味し、R2は低
級アルコキシル基、ヒドロキシル基またはハロゲ
ン原子を意味する）で表わされる化合物に関し、
この化合物は抗菌性化合物の製造原料として有用
である（特開昭59−1489号参照）。[Detailed Description of the Invention] The present invention relates to the general formula (In the formula, R 1 means a lower alkyl group, R 2 means a lower alkoxyl group, a hydroxyl group or a halogen atom)
This compound is useful as a raw material for the production of antibacterial compounds (see JP-A-59-1489).
本発明の化合物の製造法を実施例で説明する。 The method for producing the compounds of the present invention will be explained in Examples.
参考例１：原料化合物の製造
２，３−ジフルオロ−６−ニトロフエノール
7.0ｇ、エピクロルヒドリン7.0ｇ、炭酸カリウム
15ｇ及びヨウ化カリウム600mgをジメチルホルム
アミド150mlに加え、浴温85〜90℃で20時間撹拌
した。冷後不溶物を濾去し、濾液を減圧濃縮して
残渣をクロロホルムと水で分配した。クロロホル
ム層は水洗し、芒硝で乾燥後、溶媒を留去して残
渣をシリカゲルカラムクロマトグラフイで精製し
淡黄色油状物として２，３−ジフルオロ−６−ニ
トロフエニル・オキシラニルメチル・エーテル
6.1ｇを得た。Reference example 1: Production of raw material compound 2,3-difluoro-6-nitrophenol
7.0g, epichlorohydrin 7.0g, potassium carbonate
15 g and 600 mg of potassium iodide were added to 150 ml of dimethylformamide, and the mixture was stirred at a bath temperature of 85 to 90°C for 20 hours. After cooling, insoluble matters were removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was partitioned between chloroform and water. The chloroform layer was washed with water, dried over Glauber's salt, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 2,3-difluoro-6-nitrophenyl oxiranylmethyl ether as a pale yellow oil.
6.1g was obtained.
上記化合物15.0ｇおよび第二塩化スズ0.3mlを
無水メタノール60mlに加えて、２時間還流した。
溶媒を留去し残渣をクロロホルムと水で分配し、
クロロホルム層より、油状物として１−（２，３
−ジフルオロ−６−ニトロフエノキシ）−３−メ
トキシ−２−プロパノール16.1ｇを得た。 15.0 g of the above compound and 0.3 ml of tin(II) chloride were added to 60 ml of anhydrous methanol, and the mixture was refluxed for 2 hours.
The solvent was distilled off and the residue was partitioned between chloroform and water.
From the chloroform layer, 1-(2,3
16.1 g of -difluoro-6-nitrophenoxy)-3-methoxy-2-propanol was obtained.
上記化合物15ｇをアセトン150mlにとかし、氷
冷下、撹拌しつつジヨーンズ試薬（無水クロム酸
32ｇ、水64ml、濃硫酸16mlから調製）50mgを滴下
した。同温度で30分、次で室温で２時間撹拌し
た。不溶物を除却し、アセトン、次いでクロロホ
ルムで洗つて、濾液及び洗液を合せ溶媒を留去し
た。残渣はクロロホルムと水で分配し、クロロホ
ルム層を水洗し、芒硝で乾燥後クロロホルムを留
去した。残渣をシリカゲルカラムクロマトグラフ
イで精製し、クロロホルム溶出液から融点39〜42
℃の１−（２，３−ジフルオロ−６−ニトロフエ
ノキシ）−３−メトキシ−２−プロパノン10.6ｇ
を得た。 Dissolve 15 g of the above compound in 150 ml of acetone, stir under ice-cooling, and use Zion's reagent (chromic anhydride).
(prepared from 32 g, 64 ml of water, and 16 ml of concentrated sulfuric acid) was added dropwise. The mixture was stirred at the same temperature for 30 minutes and then at room temperature for 2 hours. Insoluble matter was removed, washed with acetone and then with chloroform, the filtrate and washing liquid were combined, and the solvent was distilled off. The residue was partitioned between chloroform and water, the chloroform layer was washed with water, dried over sodium sulfate, and then the chloroform was distilled off. The residue was purified by silica gel column chromatography and obtained from the chloroform eluate with a melting point of 39-42.
10.6 g of 1-(2,3-difluoro-6-nitrophenoxy)-3-methoxy-2-propanone at °C
I got it.
この化合物9.5ｇをエタノール100mlに溶かし、
ラネー・ニツケル10mlを加えて常圧で接触還元し
た。触媒を濾去し、溶媒を減圧留去後、残渣をシ
リカゲルカラムクロマトグラフイで精製し油状物
3.9ｇを得た。この油状物3.0ｇにエトキシメチレ
ンマロン酸ジエチル3.5ｇを加えて浴温105〜115
℃で２時間加熱した。冷後反応物をシリカゲルカ
ラムクロマトグラフイで精製し、融点81℃の
（７，８−ジフルオロ−３−メトキシメチル−２，
３−ジヒドロ−4H−１，４−ベンゾオキサジン
−４−イル）メチレンマロン酸ジエチル4.9ｇを
得た。 Dissolve 9.5 g of this compound in 100 ml of ethanol,
10 ml of Raney Nickel was added and catalytic reduction was carried out at normal pressure. After filtering off the catalyst and distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain an oily substance.
3.9g was obtained. Add 3.5 g of diethyl ethoxymethylenemalonate to 3.0 g of this oil and bath temperature 105-115.
Heated at ℃ for 2 hours. After cooling, the reaction product was purified by silica gel column chromatography to obtain (7,8-difluoro-3-methoxymethyl-2,
4.9 g of diethyl 3-dihydro-4H-1,4-benzoxazin-4-yl)methylenemalonate was obtained.
実施例
（７，８−ジフルオロ−３−メトキシメチル−
２，３−ジヒドロ−4H−１，４−ベンゾオキサ
ジン−４−イル）メチレンマロン酸ジエチル3.0
ｇをポリリン酸エチル20ｇに加えて浴温120〜125
℃で1.5時間加熱した。冷後氷水を加え、析出物
をクロロホルムで抽出した。抽出液は水洗し、芒
硝で乾燥後、溶媒を留去した。残渣をシリカゲル
カラムクロマトグラフイで精製し、クロロホルム
溶出分から得られた粉末を、ジクロルメタンとイ
ソプロピルエーテルの混液から再結晶して融点
238℃の微針晶として９，10−ジフルオロ−３−
メトキシメチル−７−オキソ−２，３−ジヒドロ
−7H−ピリド［１，２，３−de］［１，４］ベン
ゾオキサジン−６−カルボン酸エチル1.7ｇを得
た。Example (7,8-difluoro-3-methoxymethyl-
Diethyl 2,3-dihydro-4H-1,4-benzoxazin-4-yl)methylenemalonate 3.0
Add g to 20 g of ethyl polyphosphate and bath temperature 120-125
Heated at ℃ for 1.5 hours. After cooling, ice water was added, and the precipitate was extracted with chloroform. The extract was washed with water, dried over Glauber's salt, and then the solvent was distilled off. The residue was purified by silica gel column chromatography, and the powder obtained from the chloroform elution was recrystallized from a mixture of dichloromethane and isopropyl ether to determine the melting point.
9,10-difluoro-3- as microneedles at 238℃
1.7 g of ethyl methoxymethyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate was obtained.
元素分析値 C16H15F2NO5として
計算値 C56.64，H4.46，N4.13
分析値 C56.51，H4.44，N4.02
上記化合物1.7ｇをジクロルメタン100mlに加え
氷冷下に臭化アルミニウム6.0ｇをエタンチオー
ル10mlに溶かした溶液を適下した。室温にもどし
て３時間撹拌したのち、溶媒を留去し、残渣に氷
水を加えて不溶物を濾取した。得た白色粉末をク
ロロホルムとエタノールの混液から再結晶すると
融点268〜270℃の微針晶として９，10−ジフルオ
ロ−３−ヒドロキシメチル−７−オキソ−２，３
−ジヒドロ−7H−ピリド［１，２，３−de］
［１，４］ベンゾオキサジン−６−カルボン酸エ
チル1.1ｇが得られた。 Elemental analysis value C 16 H 15 F 2 NO 5 Calculated value C56.64, H4.46, N4.13 Analysis value C56.51, H4.44, N4.02 Add 1.7 g of the above compound to 100 ml of dichloromethane and cool on ice. A solution of 6.0 g of aluminum bromide dissolved in 10 ml of ethanethiol was added to the solution. After returning to room temperature and stirring for 3 hours, the solvent was distilled off, ice water was added to the residue, and insoluble matter was filtered off. The obtained white powder was recrystallized from a mixture of chloroform and ethanol to give 9,10-difluoro-3-hydroxymethyl-7-oxo-2,3 as microneedles with a melting point of 268-270°C.
-dihydro-7H-pyrido[1,2,3-de]
1.1 g of ethyl [1,4]benzoxazine-6-carboxylate was obtained.
元素分析値 C15H13F2NO5として
計算値 C55.39，H4.03，N4.31
分析値 C55.66，H4.23，N4.29
上記化合物400mgをクロロホルム30mlに溶かし
塩化チオニル３mlを加えて４時間還流した。反応
液を減圧乾固し、残渣をクロロホルムに溶かして
水、炭酸水素ナトリウム水溶液及び水で順次洗い
芒硝で乾燥した。溶媒を留去し、残渣をクロロホ
ルムとエタノールの混液から再結晶し、融点250
〜251℃の微針晶として３−クロロメチル−９，
10−ジフルオロ−７−オキソ−２，３−ジヒドロ
−7H−ピリドー［１，２，３−de］［１，４］ベ
ンゾオキサジン−６−カルボン酸エチル220mgを
得た。 Elemental analysis value C 15 H 13 F 2 NO 5 Calculated value C55.39, H4.03, N4.31 Analysis value C55.66, H4.23, N4.29 Dissolve 400 mg of the above compound in 30 ml of chloroform and add 3 ml of thionyl chloride. In addition, the mixture was refluxed for 4 hours. The reaction solution was dried under reduced pressure, and the residue was dissolved in chloroform, washed successively with water, an aqueous sodium bicarbonate solution, and water, and dried over sodium sulfate. The solvent was distilled off, the residue was recrystallized from a mixture of chloroform and ethanol, and the melting point was 250.
3-chloromethyl-9, as microneedles at ~251°C
220 mg of ethyl 10-difluoro-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate was obtained.
元素分析値 C15H12ClF2NO4として
計算値 C52.42，H3.52，N4.08
分析値 C52.26，H3.45，N4.10
参考例２：抗菌性化合物の製造
実施例で得た化合物200mgを無水ベンゼン30ml
に懸濁し１，８−ジアザビシクロ［５，４，０］
−７−ウンデセン（DBU）230mgを加えて１時間
還流した。冷後反応液にクロロホルムを加えて水
洗し、芒硝で乾燥した。溶媒留去後残渣をシリカ
ゲルカラムクロマトグラフイで精製し、ジクロル
メタンとイソプロピルエーテルの混液から再結晶
すると、融点258〜263℃の９，10−ジフルオロ−
３−メチレン−７−オキソ−２，３−ジヒドロ−
7H−ピリド［１，２，３−de］［１，４］ベンゾ
オキサジン−６−カルボン酸エチル120mgが得ら
れた。 Elemental analysis value C 15 H 12 ClF 2 NO 4 Calculated value C52.42, H3.52, N4.08 Analysis value C52.26, H3.45, N4.10 Reference example 2: Production of antibacterial compound In the example 200 mg of the obtained compound was added to 30 ml of anhydrous benzene.
Suspended in 1,8-diazabicyclo[5,4,0]
230 mg of -7-undecene (DBU) was added and the mixture was refluxed for 1 hour. After cooling, chloroform was added to the reaction mixture, washed with water, and dried with Glauber's salt. After evaporating the solvent, the residue was purified by silica gel column chromatography and recrystallized from a mixture of dichloromethane and isopropyl ether to give 9,10-difluoro-
3-methylene-7-oxo-2,3-dihydro-
120 mg of ethyl 7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate was obtained.
NMR（DMSO−d6，δppm）
３位メチレン基；5.47，5.89
（各1H，ｄ，Ｊ＝2.5Hz）
上記化合物100mgをジメチルスルホキシド３ml
に溶かし、Ｎ−メチルピペラジン100mgを加えて
浴温120〜130℃で６時間撹拌した。冷後溶媒を減
圧乾固し、残渣をシリカゲルカラムクロマトグラ
フイで精製した。得た粉末100mgをエタノール10
mlに懸濁し、３％水酸化ナトリウム水溶液１mlを
加えて40〜50℃で30分間撹拌した。反応液を減圧
乾固し、残渣に水を加えて希塩酸で酸性としたの
ち再び炭酸水素ナトリウムで塩基性とし、クロロ
ホルムで抽出した。抽出液は芒硝で乾燥し、溶媒
を留去した。残渣をシリカゲルカラムクロマトグ
ラフイで精製し、エタノールから再結晶すると融
点200〜201℃の微針晶として９−フルオロ−10−
（４−メチル−１−ピペラジニル）−３−メチレン
−７−オキソ−２，３−ジヒドロ−7H−ピリド
［１，２，３−de］［１，４］ベンゾオキサジン
−６−カルボン酸25mgが得られた。 NMR (DMSO-d 6 , δppm) Methylene group at 3-position; 5.47, 5.89 (1H, d, J = 2.5Hz each) 100mg of the above compound was dissolved in 3ml of dimethyl sulfoxide.
100 mg of N-methylpiperazine was added thereto, and the mixture was stirred at a bath temperature of 120 to 130°C for 6 hours. After cooling, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography. 100 mg of the obtained powder was mixed with ethanol 10
ml, 1 ml of 3% aqueous sodium hydroxide solution was added, and the mixture was stirred at 40 to 50°C for 30 minutes. The reaction solution was dried under reduced pressure, water was added to the residue, acidified with dilute hydrochloric acid, made basic again with sodium bicarbonate, and extracted with chloroform. The extract was dried with Glauber's salt and the solvent was distilled off. The residue was purified by silica gel column chromatography and recrystallized from ethanol to give 9-fluoro-10- as microneedles with a melting point of 200-201°C.
25 mg of (4-methyl-1-piperazinyl)-3-methylene-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid Obtained.
Claims (1)
級アルコキシル基、ヒドロキシル基またはハロゲ
ン原子を意味する）で表わされる化合物。[Claims] 1 formula (In the formula, R 1 means a lower alkyl group, and R 2 means a lower alkoxyl group, a hydroxyl group, or a halogen atom).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20544189A JPH02138281A (en) | 1989-08-08 | 1989-08-08 | 3-substituted pyridobenzoxazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20544189A JPH02138281A (en) | 1989-08-08 | 1989-08-08 | 3-substituted pyridobenzoxazine |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57112040A Division JPS591489A (en) | 1982-06-29 | 1982-06-29 | Pyridobenzoxazine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02138281A JPH02138281A (en) | 1990-05-28 |
| JPH0317838B2 true JPH0317838B2 (en) | 1991-03-11 |
Family
ID=16506931
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20544189A Granted JPH02138281A (en) | 1989-08-08 | 1989-08-08 | 3-substituted pyridobenzoxazine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02138281A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3487083B2 (en) * | 1996-02-09 | 2004-01-13 | 日立化成工業株式会社 | Thermosetting resin composition and cured product thereof |
-
1989
- 1989-08-08 JP JP20544189A patent/JPH02138281A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02138281A (en) | 1990-05-28 |
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