JPS5824438B2 - 2-(1-piperazinyl) pyrido (2,3-D) pyrimidine - Google Patents
2-(1-piperazinyl) pyrido (2,3-D) pyrimidineInfo
- Publication number
- JPS5824438B2 JPS5824438B2 JP49017416A JP1741674A JPS5824438B2 JP S5824438 B2 JPS5824438 B2 JP S5824438B2 JP 49017416 A JP49017416 A JP 49017416A JP 1741674 A JP1741674 A JP 1741674A JP S5824438 B2 JPS5824438 B2 JP S5824438B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- piperazinyl
- acid
- pyrimidine
- hydrogen atom
- 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
- -1 2-(1-piperazinyl) pyrido (2,3-D) pyrimidine Chemical compound 0.000 title claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000005110 aryl thio group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 claims description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 claims description 2
- 150000003230 pyrimidines Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 239000002253 acid Chemical group 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NQUXKBNPSFAQIV-UHFFFAOYSA-N 8-ethenyl-5-oxo-2-piperazin-1-ylpyrido[2,3-d]pyrimidine-6-carboxylic acid;hydrochloride Chemical compound Cl.N=1C=C2C(=O)C(C(=O)O)=CN(C=C)C2=NC=1N1CCNCC1 NQUXKBNPSFAQIV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000005452 food preservative Substances 0.000 description 1
- 235000019249 food preservative Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- YPOXGDJGKBXRFP-UHFFFAOYSA-N pyrimidine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明の目的は抗菌剤として有用な化合物およびその中
間体の製法を提供することにある。DETAILED DESCRIPTION OF THE INVENTION An object of the present invention is to provide a compound useful as an antibacterial agent and a process for producing intermediates thereof.
本発明は一般式
〔式中、Ｒ１はビニル基を意味し、Ｒ２は水素原子また
は低級アルキル基を意味し、Ｒ３は）・ロゲンで置換さ
れていることもあるアルカノイル基、アリール基で置換
されていることもあるアルコキシカルボニル基、アロイ
ル基、ホルミル基、カルバモイル基、チオカルバモイル
基、アリールもしくは低級アルキルスルホニル基、アリ
ールチオ基、トリチル基またば−ＣＨ＝ＣＨ−Ｒで表わ
される基を意味する。The present invention is based on the general formula [wherein R1 means a vinyl group, R2 means a hydrogen atom or a lower alkyl group, and R3 is an alkanoyl group which may be substituted with rogene or an aryl group] means an alkoxycarbonyl group, an aroyl group, a formyl group, a carbamoyl group, a thiocarbamoyl group, an aryl or lower alkylsulfonyl group, an arylthio group, a trityl group, or a group represented by -CH=CH-R.
ここにおいてＲは水素原子、低級アルキル基またはアリ
ール基を意味する。R here means a hydrogen atom, a lower alkyl group or an aryl group.
〕で表わされる４−保護−ピペラジン誘導体を酸または
塩基の存在下分解することにより該保護基を脱離せしめ
ることを特徴とする一般式
〔式中、偽は水素原子または低級アルキル基を意味し、
Ｒ１は前掲と同じものを意味する。The general formula is characterized in that the protecting group is removed by decomposing a 4-protected-piperazine derivative represented by ,
R1 means the same as above.
〕で表わされる２−（１−ピペラジニル）ピリド〔２・
３−ｄ〕ピリミジン誘導体およびその塩の製法に関する
。] 2-(1-piperazinyl)pyrido [2.
3-d] relates to a method for producing pyrimidine derivatives and salts thereof.
ここにおいて、Ｒ３の具体的な例としては、アセチル、
トリフルオロアセチル、ベンゾイル、ホルミル、ベンジ
ロキシカルボニル、エトキシカルボニル、ｔ−ブトキシ
カルボニルの如き保護基として普通一般に使用される酸
残基、ｐ−トルエンスルホニル、メタンスルホニルノ如
キアリールもしくは低級アルキルスルホニル基、０−ニ
トロフェニルチオ基の如きアリールチオ基またはビニル
基、１−プロペニル基等の保護基が挙げられる。Here, specific examples of R3 include acetyl,
Acid residues commonly used as protecting groups such as trifluoroacetyl, benzoyl, formyl, benzyloxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, p-toluenesulfonyl, methanesulfonyl, chiaryl or lower alkylsulfonyl groups, 0 Examples thereof include arylthio groups such as -nitrophenylthio group, and protecting groups such as vinyl group and 1-propenyl group.
本発明によれば、原料化合物ＣＩ）の保護基を脱離せし
め目的物ＣＩＮを得る。According to the present invention, the protecting group of the starting compound CI) is removed to obtain the target compound CIN.
この際、反応を促進する意味で酸または塩基触媒共存下
行なうのが一般的である。At this time, it is generally carried out in the presence of an acid or base catalyst in order to promote the reaction.
酸としては、塩酸、臭酸、ヨウ化水素酸、硫酸、リン酸
等の無機酸、酢酸、トリフルオロ酢酸、蓚酸、トルエン
スルホン酸等の有機酸が挙げられる。Examples of acids include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, and phosphoric acid, and organic acids such as acetic acid, trifluoroacetic acid, oxalic acid, and toluenesulfonic acid.
塩基としては、水酸化ナトリウム、水酸化バリウム等の
アルカリ金属の水酸化物、炭酸ナトリウム、炭酸カリウ
ム等の炭酸塩、更には酢酸ナトリウム等が挙げられる。Examples of the base include alkali metal hydroxides such as sodium hydroxide and barium hydroxide, carbonates such as sodium carbonate and potassium carbonate, and sodium acetate.
また上記酸の存在下、原料を直接加熱した後、これを水
に加える方法を採用してもよい。Alternatively, a method may be adopted in which the raw material is directly heated in the presence of the acid and then added to water.
溶媒は原料の性質により、水、含水または非水溶媒（エ
タノール、ジオキサン、エチレングリコールジメチルエ
ーテル、ベンゼン、ピリジン、酢酸等）モ使用される。Depending on the nature of the raw material, water, aqueous or nonaqueous solvents (ethanol, dioxane, ethylene glycol dimethyl ether, benzene, pyridine, acetic acid, etc.) are used as the solvent.
反応温度は２０〜１５０℃が好ましい。The reaction temperature is preferably 20 to 150°C.
本反応を実施する際、カルボン酸のエステルが加水分解
を受けることもあり、また、例えば、ホルミル、トリフ
ルオロアセチル、ｔ−ブトキシカルボニル、トリチルが
保護基である場合には、緩和な分解条件で該保護基の脱
離が起るので、他の官能基に影響を与えない。When carrying out this reaction, esters of carboxylic acids may undergo hydrolysis, and if, for example, formyl, trifluoroacetyl, t-butoxycarbonyl, or trityl is a protecting group, mild decomposition conditions may be necessary. Since the protecting group is eliminated, other functional groups are not affected.
目的物〔■〕がエステルの形で得られる場合には、常法
により加水分解してカルボン酸とすることも、さらに酸
または塩基で処理することにより、アミンの塩酸塩、硫
酸塩、蓚酸塩、酢酸塩、酒石酸塩、メタンスルホン酸塩
、またはカルボン酸のナトリウム塩、カリウム塩とする
こともできる。When the target product [■] is obtained in the form of an ester, it can be hydrolyzed to a carboxylic acid by a conventional method, or it can be further treated with an acid or a base to form a hydrochloride, sulfate, or oxalate of the amine. , acetate, tartrate, methanesulfonate, or sodium or potassium salts of carboxylic acids.
また、目的物は通常水相物の形で得られ、これを無水物
とすることもできる。Further, the target product is usually obtained in the form of an aqueous phase, and this can also be made into an anhydride.
かくして得られる目的物ＣＩＩ）およびその塩は新規化
合物であり、優れた抗菌作用を有し、医薬のみならず動
物薬、食品防腐剤として種々の形で使用される。The object product CII) and its salts thus obtained are novel compounds, have excellent antibacterial activity, and are used in various forms not only as medicines but also as veterinary medicines and food preservatives.
なお、原料化合物ＣＩ）も新規化合物であり、次の方法
により製造することができる。Note that the starting compound CI) is also a new compound and can be produced by the following method.
すなわち、例えば次の一般式 〔式中、Ｒ２およびＲ３は前掲と同じものを意味する。That is, for example, the following general formula [In the formula, R2 and R3 have the same meanings as above.
〕で表わされる化合物をクロルエチル化して得られる一
般式
〔式中、Ｒ２およびＲ３は前掲と同じものを意味する。The general formula obtained by chloroethylating a compound represented by the formula [wherein R2 and R3 have the same meanings as defined above].
〕で表わされる化合物を水酸化ナトリウムの如き塩基と
加熱し塩化水素を脱離せしめることにより製造できる。It can be produced by heating the compound represented by the above with a base such as sodium hydroxide to eliminate hydrogen chloride.
次に実施例を挙げて更に具体的に説明する。Next, a more specific explanation will be given with reference to examples.
実施例 １
５ ・８−ジヒドロ−５−オキソ−２−（ｌ−ピペラジ
ニル）−８−ビニルピリド〔２・３−ｄ）ピリミジン−
６−カルボン酸・塩酸塩の製法５・８−ジヒドロ−２−
（４−エトキシカルボニル−１−ピペラジニル）−５−
オキソ−８−ビニルピリド〔２・３−ｄ〕ピリミジン−
６−カルボン酸３．７３ ｆに１５％塩酸６０ｒｎｌお
よびエタノール３０ＴＩｌｌを加え、沸騰水浴上で３０
分間加熱還流させる。Example 1 5.8-dihydro-5-oxo-2-(l-piperazinyl)-8-vinylpyrido[2.3-d)pyrimidine-
Production method of 6-carboxylic acid hydrochloride 5, 8-dihydro-2-
(4-ethoxycarbonyl-1-piperazinyl)-5-
Oxo-8-vinylpyrido[2,3-d]pyrimidine-
Add 60 rnl of 15% hydrochloric acid and 30 tll of ethanol to 3.73 f of 6-carboxylic acid, and boil for 30 rnl on a boiling water bath.
Heat to reflux for a minute.
冷却後析出する結晶をｒ取し、エタノールで洗浄してか
ら水約１５０ｍ１に加熱して溶かし脱色炭０．６ｆを加
えしばらく加温後、濾過する。After cooling, the precipitated crystals are collected, washed with ethanol, heated to about 150 ml of water, dissolved, added with 0.6 g of decolorizing charcoal, heated for a while, and then filtered.
Ｐ液に濃塩酸８Ｉ７１１を加え放冷すると結晶が析出す
る。When concentrated hydrochloric acid 8I711 is added to the P solution and allowed to cool, crystals are precipitated.
結晶を冷水、次いでエタノールで洗い乾燥して２．３５
？の目的物を得る。The crystals were washed with cold water and then with ethanol and dried to yield 2.35
? Obtain the desired object.
融点２９８−３０１℃（分解）。Melting point 298-301°C (decomposition).
実施例 ２
５・８−ジヒドロ−５−オキソ−２−（ｌ−ピペラジニ
ル）−８−ビニルピリド〔２・３−ｄ）ピＩＪ ミジン
−６−カルボン酸エチル エステルの製法
５・８−ジヒドロ−５−オキソ−２−（４−トリフルオ
ロアセチル−１−ピペラジニル）−８−ビニルピリド〔
２・３−ｄ〕ピリミジン−６−カルボン酸エチル エス
テルＱ、８５Ｐに７％炭酸カリウム水溶液４ ｍｌ、エ
タノール４ｍ１．およびクロロホルム４１ｒＬｌを加え
、室温にて攪拌下１．５時間反応させる。Example 2 Preparation of 5,8-dihydro-5-oxo-2-(l-piperazinyl)-8-vinylpyrido[2,3-d)piIJ midine-6-carboxylic acid ethyl ester 5,8-dihydro-5 -Oxo-2-(4-trifluoroacetyl-1-piperazinyl)-8-vinylpyrido [
2.3-d] Pyrimidine-6-carboxylic acid ethyl ester Q, 85P, 4 ml of 7% potassium carbonate aqueous solution, 4 ml of ethanol. and 41 rLl of chloroform were added, and the mixture was allowed to react at room temperature for 1.5 hours with stirring.
反応後溶媒を減圧留去し、残渣をクロロホルムで抽出し
、水洗、乾燥後クロロホルムを留去し、残渣に酢酸エチ
ルを加えて結晶化せしめる。After the reaction, the solvent is distilled off under reduced pressure, the residue is extracted with chloroform, washed with water, dried, and then chloroform is distilled off, and ethyl acetate is added to the residue for crystallization.
結晶を沢取し酢酸エチルより再結晶して淡橙色針状晶の
目的物０，５ｓｙを得る。The crystals were collected and recrystallized from ethyl acetate to obtain the desired product 0.5sy in the form of light orange needles.
融点１８０−１８３℃
実施例 ３
５・８−ジヒドロ−２−（４−エトキシカルボニル−１
−ピペラジニル）−５−オキソ−８−ビニルピリド〔２
・３−ｄ、：］］ピリミジンー６−カルボン酸３７３グ
に１５％塩酸６０ ｍｌおよびエタノール３０ｍ１を加
え、沸騰水浴上で３０分間加熱還流させる。Melting point 180-183°C Example 3 5,8-dihydro-2-(4-ethoxycarbonyl-1
-piperazinyl)-5-oxo-8-vinylpyrido [2
60 ml of 15% hydrochloric acid and 30 ml of ethanol are added to 373 g of pyrimidine-6-carboxylic acid, and the mixture is heated under reflux on a boiling water bath for 30 minutes.
冷却後析出する結晶を１取し、エタノールで洗浄してか
ら水約１５０ｍ１に加熱して溶かし脱色炭０６グを加え
しばらく加温後、沢過する。After cooling, take one crystal that precipitates, wash it with ethanol, heat it in about 150 ml of water, dissolve it, add 0.6 g of decolorizing charcoal, heat it for a while, and filter it thoroughly.
涙液に濃塩酸８ｍｌを加え放冷すると結晶が析出する。When 8 ml of concentrated hydrochloric acid is added to the tear fluid and allowed to cool, crystals will precipitate.
結晶を冷水、次いでエタノールで洗い乾燥して２．３５
Ｓ’の５・８−ジヒドロ−５−オキソ−２−（ｌ−ピペ
ラジニル）−８−ビニルピリド〔２・３−ｄ〕ピリミジ
ン−６−カルボン酸・塩酸塩を得る。The crystals were washed with cold water and then with ethanol and dried to yield 2.35
5,8-dihydro-5-oxo-2-(l-piperazinyl)-8-vinylpyrido[2,3-d]pyrimidine-6-carboxylic acid hydrochloride of S' is obtained.
融点２９８−３０１°Ｃ
（分解）
前記、塩酸塩の１．５１を５％炭酸ナトリウム水溶液に
溶かし、酢酸で中和し、氷冷する。Melting point: 298-301°C (decomposition) 1.51 of the above hydrochloride was dissolved in a 5% aqueous sodium carbonate solution, neutralized with acetic acid, and cooled on ice.
析出結晶をエタノールより再結晶し、６５℃以下で乾燥
すると５・８−ジヒドロ−５−オキソ−２−（ｌ−ピペ
ラジニル）−８−ビニルピリド（２−３−ｄ〕ピリミジ
ン−６−カルボン酸水和物１．４２９を得る。The precipitated crystals are recrystallized from ethanol and dried at below 65°C to give 5,8-dihydro-5-oxo-2-(l-piperazinyl)-8-vinylpyrido(2-3-d)pyrimidine-6-carboxylic acid water. 1.429 of the compound is obtained.
この水和物を１１０℃で加熱することにより無水物を得
る。An anhydride is obtained by heating this hydrate at 110°C.
元素分析（Ｃ１４Ｈｌ ５ Ｎ５ ｏ３として）計算値
（％） Ｃ：５５．８０、Ｈ：５．０２、Ｎ：２３．
２５
実測値（％）Ｃ：５５．８８、Ｈ：５．０２、Ｎ：２３
．５４Elemental analysis (as C14Hl5N5o3) Calculated values (%) C: 55.80, H: 5.02, N: 23.
25 Actual value (%) C: 55.88, H: 5.02, N: 23
．． 54
Claims (1)
低級アルキル基を意味し、Ｒ３はハロゲンで置換されて
いることもあるアルカノイル基、アリール基で置換され
ていることもあるアルコキシカルボニル基、アロイル基
、ホルミル基、カルバモイル基、チオカルバモイル基、
アリール基もしくは低級アルキルスルホニル基、アリー
ルチオ基、トリチル基または−ＣＨ＝ＣＨ−Ｒで表わさ
れる基を意味する。 ここにおいてＲは水素原子、低級アルキル基またはアリ
ール基を意味する。 〕で表わされる化合物を酸または塩基の存在下分解する
ことを特徴とする一般式 〔式中、Ｒ′２は水素原子または低級アルキル基を意味
し、ＲＩは前掲と同じものを意味する。 〕で表わされる２−（１−ピペラジニル）ピリド〔２・
３−ｄ〕ピリミジン誘導体およびその塩の製法。[Claims] 1 General formula [In the formula, R1 means a vinyl group, R2 means a hydrogen atom or a lower alkyl group, and R3 is substituted with an alkanoyl group or an aryl group that may be substituted with a halogen. Alkoxycarbonyl group, aroyl group, formyl group, carbamoyl group, thiocarbamoyl group,
It means an aryl group, a lower alkylsulfonyl group, an arylthio group, a trityl group, or a group represented by -CH=CH-R. R here means a hydrogen atom, a lower alkyl group or an aryl group. [In the formula, R'2 means a hydrogen atom or a lower alkyl group, and RI means the same as mentioned above. ] 2-(1-piperazinyl)pyrido [2.
3-d] Method for producing pyrimidine derivatives and salts thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49017416A JPS5824438B2 (en) | 1974-02-12 | 1974-02-12 | 2-(1-piperazinyl) pyrido (2,3-D) pyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49017416A JPS5824438B2 (en) | 1974-02-12 | 1974-02-12 | 2-(1-piperazinyl) pyrido (2,3-D) pyrimidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS50111097A JPS50111097A (en) | 1975-09-01 |
| JPS5824438B2 true JPS5824438B2 (en) | 1983-05-20 |
Family
ID=11943387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP49017416A Expired JPS5824438B2 (en) | 1974-02-12 | 1974-02-12 | 2-(1-piperazinyl) pyrido (2,3-D) pyrimidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5824438B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62203941U (en) * | 1986-06-16 | 1987-12-26 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1200470B (en) * | 1985-05-10 | 1989-01-18 | Schering Spa | ANTIBACTERIAL ACTIVITY COMPOUNDS, THEIR PREPARATION AND RELATED PHARMACEUTICAL COMPOSITIONS |
| IT1201418B (en) * | 1985-05-20 | 1989-02-02 | Unibios Spa | PROCEDURE FOR THE PREPARATION OF 8-ETHYL-5,8-DIHYDRO-5-OXY-2- (1PIPERAZINYL) PYRID 2,3-D PYRAMIDIN-6-CARBOXYLIC ACID |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2338325A1 (en) * | 1972-08-02 | 1974-02-07 | Bellon Labor Sa Roger | 8-ALKYL-5-OXO-5,8-DIHYDROPYRIDO (2,3D) -PYRIMIDINE-6-CARBONIC ACIDS |
-
1974
- 1974-02-12 JP JP49017416A patent/JPS5824438B2/en not_active Expired
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2338325A1 (en) * | 1972-08-02 | 1974-02-07 | Bellon Labor Sa Roger | 8-ALKYL-5-OXO-5,8-DIHYDROPYRIDO (2,3D) -PYRIMIDINE-6-CARBONIC ACIDS |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62203941U (en) * | 1986-06-16 | 1987-12-26 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS50111097A (en) | 1975-09-01 |
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