JPS5833233B2 - Synquina pyridopyrimidine -2- - Google Patents
Synquina pyridopyrimidine -2-Info
- Publication number
- JPS5833233B2 JPS5833233B2 JP49061549A JP6154974A JPS5833233B2 JP S5833233 B2 JPS5833233 B2 JP S5833233B2 JP 49061549 A JP49061549 A JP 49061549A JP 6154974 A JP6154974 A JP 6154974A JP S5833233 B2 JPS5833233 B2 JP S5833233B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- general formula
- compound represented
- lower alkoxy
- synquina
- 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
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- IAAQUOVTPAMQCR-UHFFFAOYSA-N 1h-pyrido[3,2-d]pyrimidin-2-one Chemical class C1=CC=C2NC(=O)N=CC2=N1 IAAQUOVTPAMQCR-UHFFFAOYSA-N 0.000 claims description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 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
- 238000000034 method Methods 0.000 description 2
- -1 methoxy, ethoxy Chemical group 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- RQKUJJHLFXCIDI-UHFFFAOYSA-N [2-(3-chloroanilino)pyridin-3-yl]methanol Chemical compound OCC1=CC=CN=C1NC1=CC=CC(Cl)=C1 RQKUJJHLFXCIDI-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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】
本発明は一般式（Ｉ）
（式中、Ｒはフェニル基又はハロゲン原子、低級アルキ
ル基、ニトロ基、トリフルオロメチル基、低級アルコキ
シ基で置換されたフェニル基を意味する）で表わされる
新規なピリドピリミジン−２−オン誘導体の製造法に関
するものである。Detailed Description of the Invention The present invention is based on the general formula (I) (wherein R is a phenyl group or a phenyl group substituted with a halogen atom, a lower alkyl group, a nitro group, a trifluoromethyl group, or a lower alkoxy group) The present invention relates to a method for producing a novel pyridopyrimidin-2-one derivative represented by
更に詳しくは一般式（ｎ）
（式中、Ｒは前記と同じ意味を有する）で表わされる２
−アミノ−３−ハイドロキシメチルピリジン誘導体と一
般式（ＩＩＩ）
＊（式中二Ｒはアミノ基及び低級アルコキシ基を表わす
）で表わされる化合物とを反応させ、前記一般式（Ｉ）
で表わされる化合物を製造する方法に関するものである
。More specifically, 2 represented by the general formula (n) (wherein R has the same meaning as above)
-Amino-3-hydroxymethylpyridine derivative and a compound represented by the general formula (III) * (in the formula, two R represents an amino group and a lower alkoxy group) are reacted, and the compound represented by the general formula (I) is reacted.
The present invention relates to a method for producing a compound represented by:
前記一般式（Ｉ）におけるＲを更に具体的に説明すると
、Ｒはフェニル基、又は塩素、臭素、弗素、沃素等のハ
ロゲン原子、メチル、エチル、プロピル等の低級アルキ
ル基、メトキシ、エトキシ、プロポキシ等の低級アルコ
キシ基、ニトロ基及びトリフルオロメチル基等を任意の
位置にｌ〜２個置換したフェニル基を表わす。To explain R in the general formula (I) more specifically, R is a phenyl group, a halogen atom such as chlorine, bromine, fluorine, or iodine, a lower alkyl group such as methyl, ethyl, or propyl, methoxy, ethoxy, or propoxy. represents a phenyl group substituted with 1 to 2 lower alkoxy groups, nitro groups, trifluoromethyl groups, etc. at arbitrary positions.
又、一般式（ＩＩＩ）で表わされる化合物は具体的には
尿素、エチルウレタン、メチルウレタン等を表わす。Further, the compound represented by the general formula (III) specifically represents urea, ethyl urethane, methyl urethane and the like.
本発明の方法を反応式で示すと次の通りである。The reaction formula of the method of the present invention is as follows.
前記の反応は一般式（ＩＩ）で表わされる化合物に対し
て一般式（ｍ）で表わされる化合物を５〜１５倍モル使
用し、熱溶媒下直接加熱するか、又はエチレングリコー
ル、グロピレングリコール、ジエチレンクリコール、ジ
エチレンクリコール、ポリプロピレングリコール等のア
ルコール類の存在下加熱することによって行なわれる。The above reaction uses 5 to 15 times the mole of the compound represented by the general formula (m) relative to the compound represented by the general formula (II), and is heated directly in a hot solvent, or ethylene glycol, glopylene glycol, This is carried out by heating in the presence of an alcohol such as diethylene glycol, diethylene glycol, or polypropylene glycol.
反応温度は１５０〜２５０℃が適当であり、特に１８０
〜２３０℃が最適である。The reaction temperature is suitably 150 to 250°C, especially 180°C.
~230°C is optimal.
又、反応時間は３〜１ｏ時間で充分である。Further, a reaction time of 3 to 10 hours is sufficient.
これらの条件は他の条件を考慮し最適条件を決定すべき
であり、必ずしも前記の条件に限定されるものではない
。These conditions should be determined in consideration of other conditions, and are not necessarily limited to the above conditions.
入窒素雰囲気中で行なうと目的化合物の着色防止及びそ
の他の点で有利である。Carrying out the reaction in a nitrogen atmosphere is advantageous in preventing coloration of the target compound and in other respects.
反応生成物は冷後、水又は熱水を加え可溶性物質を除去
し、残渣をメタノール、アセトン、ジメチルホルムアミ
ド、テトラヒドロフラン等の有機溶媒で再結晶するか、
又はカラムクロマト法によって分離することによって精
製することができる。After cooling the reaction product, water or hot water is added to remove soluble substances, and the residue is recrystallized from an organic solvent such as methanol, acetone, dimethylformamide, or tetrahydrofuran, or
Alternatively, it can be purified by separation by column chromatography.
本発明により得られた化合物は文献未載の新規化合物で
あり、鎮痛作用、抗炎症作用及び中枢神経抑制作用等の
薬理活性を有し、医薬品又は医薬品の中間原料として有
用な化合物である。The compound obtained by the present invention is a new compound that has not been described in any literature, and has pharmacological activities such as analgesic action, anti-inflammatory action, and central nervous system depressing action, and is a compound useful as a drug or an intermediate raw material for a drug.
以下に実施例を示し本発明を更に具体的に説明する。EXAMPLES The present invention will be explained in more detail with reference to Examples below.
実施例 １
２−（ｍ−クロロアニリノ）−３−ハイドロキシメチル
ピリジン２３．４ｆ、尿素６０１及びジエチレングリコ
ール２５７７１１を１８０℃で４時間、次に２００℃で
５時間反応させた。Example 1 23.4f of 2-(m-chloroanilino)-3-hydroxymethylpyridine, urea 601 and diethylene glycol 257711 were reacted at 180°C for 4 hours and then at 200°C for 5 hours.
反応終了後、反応生成物を温水で洗浄し可溶性物質を除
去し残渣をメタノールより再結晶して、無色プリズム晶
の１−（ｍ−クロロフェニル）−２−オキソート２・３
・４−テトラヒドロピリド〔２・３−ｄ〕ピリミジン１
６．１ｆを得た。After completion of the reaction, the reaction product was washed with warm water to remove soluble substances, and the residue was recrystallized from methanol to obtain colorless prismatic crystals of 1-(m-chlorophenyl)-2-oxoate 2.3.
・4-tetrahydropyrido[2.3-d]pyrimidine 1
6.1f was obtained.
この物質の融点及び元素分析値は次の通りであつた。The melting point and elemental analysis values of this substance were as follows.
融点２０８〜２１０°Ｃ
元素分析値 Ｃ１３Ｈ１ｏＣＩＮ３０
理論値 Ｃ： ６１．３２ Ｈ： ３．８１Ｎ ：
１６．２４
実測値 Ｃ：６１．２８ Ｈ：３．８８Ｎ：１６．１
８
実施例 ２
２−アニリノ−２−ハイドロキシメチルピリジン６１、
尿素２７ｙ及びジエチレングリコール２５７７２１を攪
拌下１８０〜２００℃で８時間反応させた。Melting point 208-210°C Elemental analysis value C13H1oCIN30 Theoretical value C: 61.32 H: 3.81N:
16.24 Actual value C: 61.28 H: 3.88 N: 16.1
8 Example 2 2-anilino-2-hydroxymethylpyridine 61,
Urea 27y and diethylene glycol 257721 were reacted with stirring at 180 to 200°C for 8 hours.
冷後、反応生成物に水を加え析出した結晶を戸数し更に
温水にて数回洗浄後、ジメチルホルムアミドより再結晶
して、無色プリズム晶の１−フェニル−２−オキンー■
・２・３・４−テトラヒドロピリド〔２・３−ｄ〕ピリ
ミジン４．８ｒを得た。After cooling, water was added to the reaction product and the precipitated crystals were separated, washed several times with warm water, and then recrystallized from dimethylformamide to obtain colorless prismatic crystals of 1-phenyl-2-okyne.
-2,3,4-tetrahydropyrido[2,3-d]pyrimidine 4.8r was obtained.
この物質の融点及び元素分析値は次の通りであった。The melting point and elemental analysis values of this substance were as follows.
融点２５８〜２６０℃
元素分析値 Ｃ１３”１１Ｎ３０
理論値 Ｃ：６９．３２ Ｈ：４．９２Ｎ：１８．６
６
実測値 Ｃ： ６９．２７ Ｈ： ４．９ＯＮ：１８
．６８
実施例 ３〜ＩＯ
実施例１〜２の方法に準じて次表の化合物を好収率で得
た。Melting point 258-260℃ Elemental analysis value C13"11N30 Theoretical value C: 69.32 H: 4.92 N: 18.6
6 Actual value C: 69.27 H: 4.9ON:18
．． 68 Example 3-IO According to the method of Examples 1-2, the compounds shown in the following table were obtained in good yield.
Claims (1)
フルオロメチル基、低級アルコキシ基で置換されたフェ
ニル基を 意味する）で表わされる化合物と一般式 （式中、Ｗばアミノ基又は低級アルコキシ基を意味する
）で表わされる化合物を反応させることを特徴とする一
般式 （式中、Ｒは前記と同じ意味を有する）で表わされる新
規なピリドピリミジン−２−オン誘導体の製造法。[Claims] 1 general formula (wherein R means (1) a phenyl group, (2) a phenyl group substituted with a halogen atom, a lower alkyl group, a nitro group, a trifluoromethyl group, or a lower alkoxy group) A compound represented by the general formula (wherein R means an amino group or a lower alkoxy group) is reacted with a compound represented by the general formula (wherein R means an amino group or a lower alkoxy group). A method for producing a novel pyridopyrimidin-2-one derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49061549A JPS5833233B2 (en) | 1974-05-29 | 1974-05-29 | Synquina pyridopyrimidine -2- |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49061549A JPS5833233B2 (en) | 1974-05-29 | 1974-05-29 | Synquina pyridopyrimidine -2- |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS50157394A JPS50157394A (en) | 1975-12-19 |
| JPS5833233B2 true JPS5833233B2 (en) | 1983-07-18 |
Family
ID=13174300
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP49061549A Expired JPS5833233B2 (en) | 1974-05-29 | 1974-05-29 | Synquina pyridopyrimidine -2- |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5833233B2 (en) |
-
1974
- 1974-05-29 JP JP49061549A patent/JPS5833233B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS50157394A (en) | 1975-12-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Krapcho et al. | The synthesis of 6, 9‐bis [(aminoalkyl) amino] substituted benzo [g] quinoxaline‐, benzo [g] quinazoline‐and benzo‐[g] phthalazine‐5, 10‐diones via regiospecific displacements | |
| JPS5833233B2 (en) | Synquina pyridopyrimidine -2- | |
| KR101845935B1 (en) | preparation method of pyridoisoindole derivatives | |
| JPH0641135A (en) | Imidazopteridine derivative and its production | |
| US3960926A (en) | Process for preparing azasulfonium halide salts | |
| US3433802A (en) | 3-(n-lower-alkylanilino)pyrrolidines | |
| JPH061776A (en) | Production of substituted pyrazinecarbonitrile | |
| US3954797A (en) | Process for preparing azasulfonium halide salts | |
| SU486015A1 (en) | Method for preparing fused pyridinium compounds with a bridging nitrogen atom | |
| Li | Synthesis of 1-substituted and 1, 3-disubstituted 5-hydantoincarboxylates | |
| SU528848A1 (en) | Antimicrobic-active n,n'-(dithiooxalyl)-bis-g-butyrolactam and method of preparing same | |
| JPS6011712B2 (en) | Novel 4H-pyrido[2,3-d][1,3]oxazin-4-one derivative | |
| JPS604171B2 (en) | Method for producing a novel 2-anilinopyridine-3-acetic acid derivative | |
| HU190087B (en) | Process for preparing 3-phenyl-pyrrole derivatives | |
| JPS5813550B2 (en) | Sinquinapiride (4,3-D) Pyrimidinedione | |
| JPS582951B2 (en) | Sinquinapiride (2,3-D) Pyrimidinedione | |
| JPS6020387B2 (en) | Method for producing novel quinazoline derivatives | |
| JPS5813545B2 (en) | Sinquinapiride % 2 3 - D @ pyrimidinedione | |
| JPS5920674B2 (en) | Pyrido (2,3-D) Pyrimidine | |
| IL46953A (en) | Triazolo-quinolines and their preparation | |
| JPS58429B2 (en) | Synquina 2-oxo-1,2,3,4-tetrahydropyride (2,3-D) Pyrimidine | |
| JPS6159309B2 (en) | ||
| JPH0325421B2 (en) | ||
| JPS5813547B2 (en) | Cinquinapiride (2,3-D) Pyrimidinedione | |
| JPS5920675B2 (en) | Method for producing a novel pyrimido[4,5-d]pyrimidine derivative |