JPH0331710B2 - - Google Patents
Info
- Publication number
- JPH0331710B2 JPH0331710B2 JP20544089A JP20544089A JPH0331710B2 JP H0331710 B2 JPH0331710 B2 JP H0331710B2 JP 20544089 A JP20544089 A JP 20544089A JP 20544089 A JP20544089 A JP 20544089A JP H0331710 B2 JPH0331710 B2 JP H0331710B2
- Authority
- JP
- Japan
- Prior art keywords
- chloroform
- residue
- difluoro
- water
- added
- 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 11
- 125000000217 alkyl group Chemical group 0.000 claims 1
- BOSBRKBHTFSORJ-UHFFFAOYSA-N diethyl 2-[[7,8-difluoro-3-(methoxymethyl)-2,3-dihydro-1,4-benzoxazin-4-yl]methylidene]propanedioate Chemical compound C(C)OC(C(C(=O)OCC)=CN1C(COC2=C1C=CC(=C2F)F)COC)=O BOSBRKBHTFSORJ-UHFFFAOYSA-N 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 239000010446 mirabilite Substances 0.000 description 6
- 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 6
- 239000000203 mixture Substances 0.000 description 5
- -1 (7,8-difluoro-3-methoxymethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methylenemalonic acid Chemical compound 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- DCTOHCCUXLBQMS-UHFFFAOYSA-N 1-undecene Chemical compound CCCCCCCCCC=C DCTOHCCUXLBQMS-UHFFFAOYSA-N 0.000 description 3
- 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 238000003756 stirring Methods 0.000 description 3
- 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 2
- 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
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 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
- 238000010992 reflux Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 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
- 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
- XNIVKSPSCYJKBL-UHFFFAOYSA-N 2h-1,2-benzoxazine-6-carboxylic acid Chemical compound O1NC=CC2=CC(C(=O)O)=CC=C21 XNIVKSPSCYJKBL-UHFFFAOYSA-N 0.000 description 1
- PVTXJGJDOHYFOX-UHFFFAOYSA-N 2h-1,4-benzoxazine Chemical class C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 description 1
- RROQSCBOBBLOOA-UHFFFAOYSA-N C(C)OC(=O)C=1C=CC2=C(C=CNO2)C1 Chemical compound C(C)OC(=O)C=1C=CC2=C(C=CNO2)C1 RROQSCBOBBLOOA-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
- 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
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 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
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 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
- 235000011150 stannous chloride Nutrition 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
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
【発明の詳細な説明】
産業上の利用分野
本発明は抗菌性化合物の原料として有用な化合
物に関する。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to compounds useful as raw materials for antibacterial compounds.
発明の構成
本発明は（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低
級アルキルエステルに関し、このものはピリド
［１，２，３，−de］［１，４］ベンゾオキサジン
誘導体の製造原料として有用である。Structure of the Invention The present invention relates to (7,8-difluoro-3-methoxymethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methylenemalonic acid di-lower alkyl ester, which is It is useful as a raw material for producing [1,2,3,-de][1,4]benzoxazine derivatives.
本発明化合物の製造法を実施例で説明する
実施例
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
グラフイで精製して油状物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4.1ｇを得た。 Example for explaining the method for producing the compound of the present invention by way of example 1-(2,3-difluoro-6-nitrophenoxy)-3-methoxy-2-propanone (9.5 g) was dissolved in 100 ml of ethanol, and Raney Nickel (10 ml) was dissolved in 100 ml of ethanol.
was added for catalytic reduction at normal pressure. The catalyst was filtered off, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 3.9 g of an oil. Add 3.0g of this oil to diethyl ethoxymethylenemalonate.
3.5 g was added and heated at a bath temperature of 105 to 115°C for 2 hours.
After cooling, the reaction product was purified by silica gel column chromatography to obtain (7,8-difluoro-3
-methoxymethyl-2,3-dihydro-4H-1,
4.1 g of diethyl 4-benzoxazin-4-yl)methylenemalonate was obtained.
元素分析値 C18H21F2NO6として
計算値 C56.10，H5.49，N3.64
分析値 C56.25，H5.47，N3.74
参考例 １
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
する。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する。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。 Elemental analysis value C 18 H 21 F 2 NO 6 Calculated value C56.10, H5.49, N3.64 Analysis value C56.25, H5.47, N3.74 Reference example 1 2,3-difluoro-6-nitro phenol
7.0g, epichlorohydrin 7.0g, potassium carbonate
15 g and 600 mg of potassium iodide are added to 150 ml of dimethylformamide and stirred for 20 hours at a bath temperature of 85-90°C. 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- as a pale yellow oil.
Nitrophenyl oxiranyl methyl ether
6.1g was obtained.
この化合物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時間還流する。浴
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 this compound and 0.3 ml of tin(II) chloride were added to 60 ml of anhydrous methanol and refluxed for 2 hours. The bath medium was distilled off, the residue was partitioned between chloroform and water, and from the chloroform layer, 1-(2,3-
16.1 g of difluoro-6-nitrophenoxy)-3-methoxy-2-propanol was obtained.
この化合物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）50mlを滴下
し同温度で30分、次いで室温で２時間撹拌する。
不溶物を除去し、アセトン、次いでクロロホルム
で洗つて、濾液及び洗液を合わせ溶媒を留去す
る。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
去する。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 this 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 and stirred at the same temperature for 30 minutes, then at room temperature for 2 hours.
Insoluble matter is removed, washed with acetone and then with chloroform, the filtrate and washing liquid are combined, and the solvent is distilled off. The residue was partitioned between chloroform and water, the chloroform layer was washed with water, dried over Glauber's salt, and 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.
参考例 ２
（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時間加熱する。冷後、氷水を加え、析出
物をクロロホルムで抽出する。抽出液は水洗し、
芒硝乾燥後溶媒を留去する。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
出分から得られる粉末を、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。Reference example 2 (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
Heat for 1.5 hours at °C. After cooling, ice water is added and the precipitate is extracted with chloroform. Wash the extract with water,
After drying the Glauber's salt, the solvent is distilled off. The residue was purified by silica gel column chromatography, and the powder obtained from the chloroform eluate was recrystallized from a mixture of dichloromethane and isopropyl ether to give a melting point of 238.
9,10-difluoro-3-methoxymethyl-7-oxo-2,3-dihydro- as microneedles at °C
1.7 g of ethyl 7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate was obtained.
上記化合物1.7ｇをジクロルメタン100mlに加え
て氷冷下に臭化アルミニウム6.0ｇをエタンチオ
ール10mlに溶かした溶液を滴下する。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する。得られた白色粉
末をクロルホルムとエタノールの混液から再結晶
して融点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を得た。 1.7 g of the above compound was added to 100 ml of dichloromethane, and a solution of 6.0 g of aluminum bromide dissolved in 10 ml of ethanethiol was added dropwise under ice cooling. 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- as microneedles with a melting point of 268-270°C.
2,3-dihydro-7H-pyrido[1,2,3-
1.1 g of ethyl de][1,4]benzoxazine-6-carboxylate was obtained.
上記化合物400mgをクロロホルム30mlに溶かし
これに塩化チオニル３mlを加えて４時間還流し、
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、芒硝で乾燥する。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て融
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［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。 Dissolve 400 mg of the above compound in 30 ml of chloroform, add 3 ml of thionyl chloride, and reflux 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 Glauber's salt. The solvent was distilled off, and the residue was recrystallized from a mixture of chloroform and ethanol to form 3-chloromethyl-
9,10-difluoro-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]
Ethyl benzoxazine-6-carboxylate 220mg
I got it.
上記化合物200mgを無水ベンゼン30mlに懸濁さ
せ、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
する。冷後反応液にクロロホルムを加えて水洗
し、芒硝乾燥後溶媒を留去し、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して
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を得た。 200 mg of the above compound was suspended in 30 ml of anhydrous benzene, and 1,8-diazabicyclo[5,4,0]-7
- Add 230 mg of undecene (DBU) and reflux for 1 hour. After cooling, chloroform was added to the reaction mixture and washed with water. After drying with Glauber's salt, the solvent was distilled off. The residue was purified by silica gel column chromatography, and recrystallized from a mixture of dichloromethane and isopropyl ether to give a 9. , 120 mg of ethyl 10-difluoro-3-methylene-7-oxo-2,3-dihydro-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時間撹拌する。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
ラフイで精製する。得られた粉末100mgをエタノ
ール10ml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分間撹拌する。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する。抽出液は芒硝で乾燥
し、溶媒を留去する。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
して融点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を得た。 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.
Add 100 mg of N-methylpiperazine and stir at a bath temperature of 120-130°C for 6 hours. After cooling, the solvent is dried under reduced pressure, and the residue is purified by silica gel column chromatography. 100 mg of the obtained powder is suspended in 10 ml of ethanol, 1 ml of 3% aqueous sodium hydroxide solution is added, and the mixture is 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, and then made basic again with sodium hydrogen carbonate.
Extract 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-(4-methyl-1-piperazinyl)-3-methylene-7-oxo as microneedles with a melting point of 200-201°C. -2,3-dihydro-7H-
25 mg of pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid was obtained.
NMR（CDCl3，δppm）
4.83（2H，ｓ，２位CH2）
5.26，5.61（（各1H，ｄ，Ｊ＝3.0Hz，３位
Ｃ＝CH2）
8.83（1H，ｓ，５位 Ｈ）
7.63（1H，ｄ，Ｊ＝12Hz，８位Ｈ） NMR (CDCl 3 , δppm) 4.83 (2H, s, 2nd place CH 2 ) 5.26, 5.61 ((each 1H, d, J = 3.0Hz, 3rd place
C=CH 2 ) 8.83 (1H, s, 5th H) 7.63 (1H, d, J=12Hz, 8th H)
Claims (1)
−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で
ある特許請求の範囲第１項の化合物。[Claims] 1 formula (In the formula, R 1 means a lower alkyl group.) A compound represented by: 2. The compound of claim 1 which is diethyl (7,8-difluoro-3-methoxymethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methylenemalonate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20544089A JPH02138268A (en) | 1989-08-08 | 1989-08-08 | Benzoxazine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20544089A JPH02138268A (en) | 1989-08-08 | 1989-08-08 | Benzoxazine compound |
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 |
|---|---|
| JPH02138268A JPH02138268A (en) | 1990-05-28 |
| JPH0331710B2 true JPH0331710B2 (en) | 1991-05-08 |
Family
ID=16506912
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20544089A Granted JPH02138268A (en) | 1989-08-08 | 1989-08-08 | Benzoxazine compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02138268A (en) |
-
1989
- 1989-08-08 JP JP20544089A patent/JPH02138268A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02138268A (en) | 1990-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4777253A (en) | Process for preparation of racemate and optically active ofloxacin and related derivatives | |
| JPH0566945B2 (en) | ||
| FI91070C (en) | Improvement in the synthesis of 6-methylene derivatives of androsta-1,4-diene-3,17-dione | |
| KR0125115B1 (en) | Method for preparing (-) piperazine benzoxazine derivative | |
| JPH0148911B2 (en) | ||
| JPH027314B2 (en) | ||
| JPS62252790A (en) | Pyridobenzoxazine derivative | |
| KR900004145B1 (en) | Process for preparation of tricyclic compounds | |
| JPH0331710B2 (en) | ||
| CZ294957B6 (en) | Process for preparing a substituted imidazopyridine compound | |
| JPH0518816B2 (en) | ||
| JPH0116837B2 (en) | ||
| JPH0317838B2 (en) | ||
| CS202069B2 (en) | Method of preparing 2-/4-substituted piperazine-1-yl/-4-amino-6,7-dimethoxyquinazolines | |
| WO2000015596A1 (en) | Processes for the preparation of fluorinated benzoic acids | |
| JPWO2000015596A1 (en) | Method for producing fluorine-substituted benzoic acids | |
| KR100248370B1 (en) | Preparation of intermediate of (-)-3(s)-methylpyrido benzoxizine derivative | |
| JPS6257636B2 (en) | ||
| KR960010351B1 (en) | Method for preparing benzoxazine derivatives | |
| KR0128029B1 (en) | Method for preparing benzoxazine carboxylic acid derivative | |
| DK158268B (en) | Procedure for production of pyridobenzoxazine-derivatives | |
| JP4055246B2 (en) | 5-chloro-6- (α-fluoroalkyl) -4-pyrimidone and process for producing the same | |
| JPS61246172A (en) | Benzoxazinylmalonic acid derivative | |
| JPS6256154B2 (en) | ||
| JPS61271292A (en) | 3-fluoromethyl-pyridobenzoxazine derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 19911112 |