JPS584033B2 - Method for producing a novel pyrido[2,3-d]pyrimidine-2-thione derivative - Google Patents
Method for producing a novel pyrido[2,3-d]pyrimidine-2-thione derivativeInfo
- Publication number
- JPS584033B2 JPS584033B2 JP56065721A JP6572181A JPS584033B2 JP S584033 B2 JPS584033 B2 JP S584033B2 JP 56065721 A JP56065721 A JP 56065721A JP 6572181 A JP6572181 A JP 6572181A JP S584033 B2 JPS584033 B2 JP S584033B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- pyrimidine
- general formula
- halogen atom
- producing
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- ZXNZJQFMIDCYMA-UHFFFAOYSA-N 1h-pyrido[2,3-d]pyrimidine-2-thione Chemical class C1=CC=NC2=NC(S)=NC=C21 ZXNZJQFMIDCYMA-UHFFFAOYSA-N 0.000 title description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- -1 vinyloxy group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 102100027876 Homeobox protein Nkx-2.6 Human genes 0.000 claims 1
- 101000632193 Homo sapiens Homeobox protein Nkx-2.6 Proteins 0.000 claims 1
- 241001061127 Thione Species 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 150000002736 metal compounds Chemical class 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VKXUCROJMDAHJO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine Chemical compound C1=CN=C2NCNCC2=C1 VKXUCROJMDAHJO-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HXKWWDAWOMOFHB-UHFFFAOYSA-N 2-anilinopyridine-3-carboxamide Chemical class NC(=O)C1=CC=CN=C1NC1=CC=CC=C1 HXKWWDAWOMOFHB-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 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
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-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
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000009835 boiling Methods 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 230000000881 depressing effect Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 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
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- FXLNRUXSWBZWKQ-UHFFFAOYSA-N n-methyl-2-(3-nitroanilino)pyridine-3-carboxamide Chemical compound CNC(=O)C1=CC=CN=C1NC1=CC=CC([N+]([O-])=O)=C1 FXLNRUXSWBZWKQ-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 239000008096 xylene Substances 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（■）
（式中、Ｒ１ は（１）フェニル基、又は（２）ハロゲ
ン原子、ニトロ基又はトリフルオロメチル基から選択さ
れた置換基が任意の位置に置換したフエニル基を、Ｒ２
は（１）低級アルキル基、（２）アルケニル基、（３）
アルキニル基、（４）−・ロゲン原子、水酸基、アルコ
キシ基、アセトキシ基、ビニルオキシ基、シクロアルキ
ル基、又はフエニル基から選択された置換基が置換した
低級アルキル基を意味する）で表わされる新規なピリド
〔２・３−ｄ〕ピリミジンー２−チ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 (■) (wherein R1 is (1) a phenyl group, or (2) a substituent selected from a halogen atom, a nitro group, or a trifluoromethyl group). The phenyl group substituted at the position R2
(1) lower alkyl group, (2) alkenyl group, (3)
(means a lower alkyl group substituted with a substituent selected from an alkynyl group, a (4)-rogen atom, a hydroxyl group, an alkoxy group, an acetoxy group, a vinyloxy group, a cycloalkyl group, or a phenyl group). The present invention relates to a method for producing a pyrido[2,3-d]pyrimidine-2-thione derivative.
更に詳しくは、一般式（Ｉ）
（式中、Ｒ１及びＲ２は前記と同じ意味を有する）で表
わされる２−アニリノニコチン酸アミド誘導体に一般式
（■）
（式中、Ｘはハロゲン原子及びイミダゾール基を意味す
る）で表わされる化合物（例えばチオホスゲン、１・１
−チオカルボニルジイミダゾール等）を反応させて前記
一般式（■）の新規なピリド〔２・３−ｄ〕ピリミジン
ー２−チオン誘導体を得る製造法に関するものである。More specifically, the 2-anilinonicotinamide derivative represented by the general formula (I) (wherein R1 and R2 have the same meanings as above) is combined with the general formula (■) (wherein, X is a halogen atom and imidazole group) (e.g. thiophosgene, 1.1
-thiocarbonyldiimidazole, etc.) to obtain a novel pyrido[2.3-d]pyrimidine-2-thione derivative of the general formula (■).
前記一般式（Ｉ）及び（■）において、Ｒ１及びＲ２に
ついて更に詳細に説明すると、Ｒ１の「ハロゲン原子、
ニトロ基又はトリフルオロメチル基が置換したフエニル
基」とは塩素、臭素、弗素、沃素等のハロゲン原子、ニ
トロ基又はトリフルオロメチル基等を任意の位置に１〜
２個置換したフエニル基を表わし、Ｒ２の低級アルキ４
はメチル、エチル、プロピル、ブチル、ヘキシル等を、
アルケニル基はアリル、２−メチルアリル等を、アルキ
ニル基はグロパルギル等を表わす。In the general formulas (I) and (■), R1 and R2 will be explained in more detail.
"Phenyl group substituted with nitro group or trifluoromethyl group" means a halogen atom such as chlorine, bromine, fluorine, iodine, nitro group or trifluoromethyl group, etc. at any position from 1 to
Represents a 2-substituted phenyl group, and lower alkyl 4 of R2
is methyl, ethyl, propyl, butyl, hexyl, etc.
The alkenyl group represents allyl, 2-methylallyl, etc., and the alkynyl group represents glopargyl, etc.
本発明の方法を反応式で示せば次の通りである。The reaction formula of the method of the present invention is as follows.
本発明における反応は一般にテトラヒドロフラン、ジメ
チルホルムアミド、ジオキサン、ジグリム、ベンゼン、
トルエン、キシレン、アルコール等の不活性溶媒中で行
なわれるが、金属ナトリウム、金属カリウム、水素化ナ
トリウム、ナトリウムアミド、ナトリウムアルコラート
等のアルカリ金属及び金属化合物、ピリジン、トリアル
キルアミン等の有機塩基、又は水酸化アルカリ、炭酸ア
ルカリ等の無機塩基の存在下で行なうのが好ましく、特
に上記アルカリ金属及び金属化合物を使用すると極めて
好収量で目的化合物を得ることができる。The reaction in the present invention generally involves tetrahydrofuran, dimethylformamide, dioxane, diglyme, benzene,
It is carried out in an inert solvent such as toluene, xylene, alcohol, etc., but it is also possible to use alkali metals and metal compounds such as sodium metal, potassium metal, sodium hydride, sodium amide, sodium alcoholate, organic bases such as pyridine, trialkylamines, etc. It is preferable to carry out the reaction in the presence of an inorganic base such as an alkali hydroxide or an alkali carbonate. Particularly when the above-mentioned alkali metals and metal compounds are used, the target compound can be obtained in an extremely good yield.
反応温度はチオホスゲンを使用する時は水冷下で行なう
のが好ましく、又１・１−チオ力ルポニルジイミダゾー
ルを使用する時は使用する溶媒の沸点下で一般に行なわ
れる。The reaction temperature is preferably carried out under water cooling when thiophosgene is used, and is generally carried out at the boiling point of the solvent used when 1,1-thioluponyldiimidazole is used.
生成した反応混合物は、これから有機溶媒を留去し残渣
に水を加え析出した結晶を沢取し、アセトン、メタノー
ル等の有機溶媒より再結晶すると純品を得ることができ
る。A pure product can be obtained from the generated reaction mixture by distilling off the organic solvent, adding water to the residue, collecting the precipitated crystals, and recrystallizing them from an organic solvent such as acetone or methanol.
本発明によって得られる化合物は、いずれも文献未載の
新規化合物であり、且つ顕著な鎮痛作用、抗炎症作用及
び中枢神経抑匍昨用を有し医薬品として産業上有用な化
合物である。The compounds obtained by the present invention are all new compounds that have not been published in any literature, and have significant analgesic effect, anti-inflammatory effect, and central nervous system depressing effect, and are industrially useful compounds as pharmaceuticals.
以下に本発明の実施例を示す。Examples of the present invention are shown below.
実施例 １
２−（ｍ−ニトロアニリノ）ニコチン酸メチルアミド１
．２５ｇとテトラヒドロフラン２０ｍｌの溶液に約５０
％水素化ナトリウム０． ４ ８ｇを加え、３０分間攪
拌後チオホスゲン２３グを水冷下に徐徐に滴下したのち
室温で３０分間放置した。Example 1 2-(m-nitroanilino)nicotinic acid methylamide 1
．． Approximately 50 g in a solution of 25 g and 20 ml of tetrahydrofuran
% Sodium Hydride 0. After stirring for 30 minutes, 23 g of thiophosgene was slowly added dropwise while cooling with water, and the mixture was left at room temperature for 30 minutes.
次に過剰のチオホスゲンをメタノールーアンモニア溶液
で分解後、減圧下溶媒を留去し残渣に水を加えて結晶を
析出させ、析出した結晶をアセトンより再結晶すると、
淡黄色プリズム晶の１−（ｍ−ニトロフエニル）−３−
メチル−２−チオ−４−オキソ−１・２・３・４−テト
ラヒドロピリド〔２・３−ｄ〕ピリミジン１．５ｇを得
た。Next, after decomposing excess thiophosgene with a methanol-ammonia solution, the solvent was distilled off under reduced pressure, water was added to the residue to precipitate crystals, and the precipitated crystals were recrystallized from acetone.
Pale yellow prismatic crystals of 1-(m-nitrophenyl)-3-
1.5 g of methyl-2-thio-4-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine 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２６５−２６６℃
元素分析値Ｃ１４Ｈ１０Ｎ４Ｏ３Ｓ
理論値Ｃ：５３．５１Ｈ：３．２１
Ｎ：１７．８３
実測値Ｃ：５３．６３Ｈ：３．１９
Ｎ：１７．６９
実施例２
２−（ｍ−ブロムアニリノ）ニコチン酸エチルアミド３
．２ｇとテトラヒドロフラン５０ｍｌの溶液に５０％の
水素化ナトリウム１．０５ｇを加え室温で１５分間攪拌
した。Melting point 265-266°C Elemental analysis value C14H10N4O3S Theoretical value C: 53.51H: 3.21 N: 17.83 Actual value C: 53.63H: 3.19 N: 17.69 Example 2 2-(m-bromoanilino ) Nicotinic acid ethylamide 3
．． 1.05 g of 50% sodium hydride was added to a solution of 2 g and 50 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 15 minutes.
次にチオホスゲンの３，４５１を適量のテトラヒドロフ
ランに希釈し氷冷下徐徐に滴下した。Next, 3,451 thiophosgene was diluted with an appropriate amount of tetrahydrofuran and slowly added dropwise under ice cooling.
滴下後室温で３０分間攪拌し、次いでメタノール−アン
モニア飽和溶液で水冷下過剰のチオホスゲンを分解した
。After the dropwise addition, the mixture was stirred at room temperature for 30 minutes, and then excess thiophosgene was decomposed with a methanol-ammonia saturated solution under water cooling.
その後溶媒を留去し残渣に氷水を加え析出した結晶をメ
タノールより再結晶して、無色針状晶の１−（ｍ−プロ
ムフエニル）−３−エチル−２−チオ−４−オキソ−１
・２・３・４−テトラヒドロピリド〔２・３−ｄ〕ピリ
ミジン３．２ｇを得た。Thereafter, the solvent was distilled off, ice water was added to the residue, and the precipitated crystals were recrystallized from methanol to give colorless needle-like crystals of 1-(m-promphenyl)-3-ethyl-2-thio-4-oxo-1.
- 3.2 g of 2,3,4-tetrahydropyrido[2,3-d]pyrimidine 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１８２−１８３℃
元素分析値Ｃ１５Ｈ１２Ｎ３ＢｒＯＳ
理論値Ｃ：４９．７４Ｈ：３．３４
Ｎ：１１．６０
実測値Ｃ：４９．７８Ｈ：３．３１
Ｎ：１１．５９
実施例３
２−（ｍ−トリノルオロメチルアニリノ）ニコチン酸エ
チルアミド３．ｌｇをテトラヒドロフラン５０ｍｌに溶
解後５０％水素化ナトリウム１１を加え１５分間攪拌後
、１・１−チオ力ルポニルジイミダゾール５．７１を加
え室温で１時間攪拌し、次いで還流下に５時間反応せし
めた。Melting point 182-183°C Elemental analysis value C15H12N3BrOS Theoretical value C: 49.74H: 3.34 N: 11.60 Actual value C: 49.78H: 3.31 N: 11.59 Example 3 2-(m-torino (fluoromethylanilino)nicotinic acid ethylamide 3. After dissolving 50% sodium hydride in 50 ml of tetrahydrofuran, 11 ml of 50% sodium hydride was added, and after stirring for 15 minutes, 5.71 g of 1,1-thioluponyldiimidazole was added, stirred for 1 hour at room temperature, and then reacted under reflux for 5 hours. Ta.
反応終了後、減圧下に溶媒を留去し残渣に氷水を加え析
出した結晶をメタノールより再結晶して、無色プリズム
晶（７）１−（ｍ−トリフルオロメチルフエニル）−３
−エチル−２−チオー４−オキソ−１・２・３・４−テ
トラヒドロピリド〔２・３−ｄ〕ピリミジン２．４ｇを
得た。After the reaction, the solvent was distilled off under reduced pressure, ice water was added to the residue, and the precipitated crystals were recrystallized from methanol to give colorless prism crystals (7) 1-(m-trifluoromethylphenyl)-3.
2.4 g of -ethyl-2-thio-4-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine 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１５８−１５９℃
元素分析値Ｃ１６Ｈ１２Ｆ３Ｎ３ＯＳ
理論値Ｃ：５４．７０Ｈ：３．４４
Ｎ：１１．９６
実測値Ｃ：５４．６９Ｈ：３．４８
Ｎ：１２．０１
実施例４〜４６
実施例１〜３の方法に準じて次表に示す化合物を好収率
で得た。Melting point 158-159°C Elemental analysis value C16H12F3N3OS Theoretical value C: 54.70H: 3.44 N: 11.96 Actual value C: 54.69H: 3.48 N: 12.01 Examples 4-46 Examples 1- According to method 3, the compounds shown in the following table were obtained in good yield.
Claims (1)
ン原子、ニトロ基又はトリフルオロメチル基かラ選択さ
れた置換基が任意の位置に置換したフエニル基を Ｒ２
は（１）低級アルキル基、（２）アルケニル基、（３）
アルキニル基、又は（４）ハロゲン原子、水酸基、アル
コキシ基、アセトキシ基、ビニルオキシ基、シクロアル
キル基、又はフエニル基から選択された置換基が置換し
た低級アルキル基を意味する）で表わされる２−アニリ
ノニコチン酸アミド誘導体に一般式（■） ＣＳＸ２ （■） （式中、Ｘはハロゲン原子及びイミダゾール基を意味す
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、Ｒ１及びＲ２は前記と同じ意味を有する）で表
わされる新規なピリド〔２・３−ｄ〕ピリミジン−２−
チオン誘導体の製造法。[Scope of Claims] 1 General formula (I) (wherein R1 is a substituent selected from (1) a phenyl group, or (2) a halogen atom, a nitro group, or a trifluoromethyl group, at any position) The substituted phenyl group is R2
(1) lower alkyl group, (2) alkenyl group, (3)
2-aniline represented by an alkynyl group, or (4) a lower alkyl group substituted with a substituent selected from a halogen atom, a hydroxyl group, an alkoxy group, an acetoxy group, a vinyloxy group, a cycloalkyl group, or a phenyl group. General formula (■) characterized by reacting a linonicotinic acid amide derivative with a compound represented by general formula (■) CSX2 (■) (in the formula, X means a halogen atom and an imidazole group) (in the formula , R1 and R2 have the same meanings as above).
Method for producing thione derivatives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56065721A JPS584033B2 (en) | 1981-04-28 | 1981-04-28 | Method for producing a novel pyrido[2,3-d]pyrimidine-2-thione derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56065721A JPS584033B2 (en) | 1981-04-28 | 1981-04-28 | Method for producing a novel pyrido[2,3-d]pyrimidine-2-thione derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56164189A JPS56164189A (en) | 1981-12-17 |
| JPS584033B2 true JPS584033B2 (en) | 1983-01-24 |
Family
ID=13295159
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56065721A Expired JPS584033B2 (en) | 1981-04-28 | 1981-04-28 | Method for producing a novel pyrido[2,3-d]pyrimidine-2-thione derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS584033B2 (en) |
-
1981
- 1981-04-28 JP JP56065721A patent/JPS584033B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56164189A (en) | 1981-12-17 |
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