JP2685896B2 - Cyclopenta [d] pyrimidine derivative and process for producing the same - Google Patents
Cyclopenta [d] pyrimidine derivative and process for producing the sameInfo
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- JP2685896B2 JP2685896B2 JP11648389A JP11648389A JP2685896B2 JP 2685896 B2 JP2685896 B2 JP 2685896B2 JP 11648389 A JP11648389 A JP 11648389A JP 11648389 A JP11648389 A JP 11648389A JP 2685896 B2 JP2685896 B2 JP 2685896B2
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- cyclopenta
- dihydro
- acetoxy
- pyrimidin
- reaction
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Description
【発明の詳細な説明】 〔発明の目的〕 本発明は式（Ｉ） で表わされる新規物質７−アセトキシ−6,7−ジヒドロ
−3H,5H−シクロペンタ〔ｄ〕ピリミジン−４−オンお
よびその製造法に関し、更に詳しくは、抗うつ剤および
脳障害改善剤として有用な４−（４−シアノアニリノ）
−6,7−ジヒドロ−７−ヒドロキシ−5H−シクロペンタ
〔ｄ〕ピリミジン（特開昭62-70および特開昭63-183532
参照）の合成中間体として有用な７−アセトキシ−6,7
−ジヒドロ−3H,5H−シクロペンタ〔ｄ〕ピリミジン−
４−オンおよびその製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION Object of the Invention The present invention provides compounds of formula (I) The novel substance 7-acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one represented by and its production method are described in more detail. Useful as antidepressant and cerebral disorder ameliorating agent -(4-cyanoanilino)
-6,7-Dihydro-7-hydroxy-5H-cyclopenta [d] pyrimidine (JP-A-62-70 and JP-A-63-183532)
7-acetoxy-6,7 useful as a synthetic intermediate of
-Dihydro-3H, 5H-cyclopenta [d] pyrimidine-
The present invention relates to 4-one and its manufacturing method.
抗うつ剤および脳障害改善剤として有用な４−（４−
シアノアニリノ）−6,7−ジヒドロ−７−ヒドロキシ−5
H−シクロペンタ〔ｄ〕ピリミジン（化合物VII）の製造
法として下記Ａ法とＢ法が開示されている（特開昭62-7
0、特開昭63-183532）。4- (4-, which is useful as an antidepressant and a brain disorder improving agent
Cyanoanilino) -6,7-dihydro-7-hydroxy-5
The following methods A and B have been disclosed as methods for producing H-cyclopenta [d] pyrimidine (compound VII) (JP-A-62-7).
0, JP-A-63-183532).
しかし、Ａ法には（Ｖ）から（VI）への反応工程の収
率が低いうえに、5-OAc異性体が副生し、目的物7-OAc体
（VI）との分離が困難であるという欠点があり、 また、Ｂ法には（IV）から（VIII）への酸化工程で爆
発の危険性があって実用的な製造法にはなり難いという
欠点があるため、これに代わる安全かつ経済的な製造ル
ートおよびそれを可能にする新規な中間体の開発が強く
望まれていた。 However, in method A, the yield of the reaction step from (V) to (VI) is low, and the 5-OAc isomer is by-produced, making it difficult to separate it from the desired 7-OAc compound (VI). In addition, the method B has a drawback that it is difficult to be a practical manufacturing method due to the risk of explosion in the oxidation process from (IV) to (VIII), and thus it is an alternative safety method. There has been a strong demand for the development of an economical production route and a new intermediate which enables the production route.
本発明者らはかかる現状に鑑み、鋭意検討を重ねた結
果、新規物質７−アセトキシ−6,7−ジヒドロ−3H,5H−
シクロペンタ〔ｄ〕ピリミジン−４−オン（Ｉ）が上記
化合物（VII）製造の重要な中間体になることを見い出
し、その製造法をも確立して本発明を完成するに至っ
た。The present inventors have conducted intensive studies in view of the present situation, and as a result, have found that the novel substance 7-acetoxy-6,7-dihydro-3H, 5H-
It was found that cyclopenta [d] pyrimidin-4-one (I) was an important intermediate in the production of the compound (VII), and the production method was established to complete the present invention.
本発明の新規物質７−アセトキシ−6,7−ジヒドロ−3
H,5H−シクロペンタ〔ｄ〕ピリミジン−４−オン（Ｉ）
は、７−メトキシ−6,7−ジヒドロ−3H,5H−シクロペン
タ〔ｄ〕ピリミジン−４−オン（II）を酸の存在下で無
水酢酸と反応させることによって高収率でしかも高純度
で得られる。Novel substance of the present invention 7-acetoxy-6,7-dihydro-3
H, 5H-cyclopenta [d] pyrimidin-4-one (I)
Is obtained in high yield and high purity by reacting 7-methoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one (II) with acetic anhydride in the presence of an acid. To be
反応に使用する無水酢酸は通常基質である７−メトキ
シ−6,7−ジヒドロ−3H,5H−シクロペシンタ〔ｄ〕ピリ
ミジン−４−オン（II）に対して、1.0〜50倍モルであ
り、好ましくは1.0〜20倍モルである。触媒として用い
る酸としてはブレンステッド酸およびルイス酸ともに使
用可能であり、特に限定されないが、ブレンステッド酸
としては硫酸、リン酸、ポリリン酸、トリフルオロ酢
酸、トリフルオロメタンスルホン酸、ホウ酸などが好ま
しく、ルイス酸としては塩化亜鉛、塩化アルミニウム、
塩化第二鉄、酸化ホウ素、三フッ化ホウ素およびそのコ
ンプレックス（例えば三フッ化ホウ素・ジエチルエーテ
ル コンプレックス、三フッ化ホウ素・酢酸コンプレッ
クスなど）、ボロントリアセテート、ボロントリス（ト
リフルオロアセテート）などが好ましい。これらの触媒
の使用量は通常0.1〜20倍モル、好ましくは１〜10倍モ
ルである。 The acetic anhydride used in the reaction is usually 1.0 to 50 times by mole with respect to the substrate 7-methoxy-6,7-dihydro-3H, 5H-cyclopecinta [d] pyrimidin-4-one (II), and is preferably Is 1.0 to 20 times mol. As the acid used as the catalyst, both Bronsted acid and Lewis acid can be used, and are not particularly limited, but as the Bronsted acid, sulfuric acid, phosphoric acid, polyphosphoric acid, trifluoroacetic acid, trifluoromethanesulfonic acid, boric acid and the like are preferable. , As the Lewis acid, zinc chloride, aluminum chloride,
Ferric chloride, boron oxide, boron trifluoride and complexes thereof (for example, boron trifluoride / diethyl ether complex, boron trifluoride / acetic acid complex, etc.), boron triacetate, boron tris (trifluoroacetate) and the like are preferable. The amount of these catalysts to be used is generally 0.1 to 20 times mol, preferably 1 to 10 times mol.
また、反応の促進または収率の改善を目的に無水トリ
フルオロ酢酸あるいは酢酸ナトリウム、酢酸カリウム等
のアルカリ金属酢酸塩を添加することもできる。Further, trifluoroacetic anhydride or an alkali metal acetate such as sodium acetate or potassium acetate may be added for the purpose of accelerating the reaction or improving the yield.
反応溶媒は必ずしも使用する必要はないが、使用する
場合には、反応に不活性なものであれば特に限定されな
い。好ましい溶媒としてはジクロロメタン、ジクロロエ
タン、クロロホルム等のハロゲン化炭化水素系溶媒、ベ
ンゼン、トルエン、ヘキサン等の炭化水素系溶媒および
酢酸などが挙げられる。反応温度としては−20°〜200
℃で適宜選ばれるが、好ましくは０°〜150℃である。The reaction solvent is not necessarily used, but when used, it is not particularly limited as long as it is inert to the reaction. Preferred examples of the solvent include halogenated hydrocarbon solvents such as dichloromethane, dichloroethane and chloroform, hydrocarbon solvents such as benzene, toluene and hexane, and acetic acid. The reaction temperature is -20 ° to 200
The temperature is appropriately selected at 0 ° C, but is preferably 0 ° to 150 ° C.
反応終了後、７−アセトキシ−6,7−ジヒドロ−3H,5H
−シクロペンタ〔ｄ〕ピリミジン−４−オンを反応系か
ら回収する方法としては従来公知の方法、例えば溶媒抽
出法、再結晶法、カラムクロマトグラフィーなど適宜採
用することにより行なうことができる。After completion of the reaction, 7-acetoxy-6,7-dihydro-3H, 5H
As a method for recovering -cyclopenta [d] pyrimidin-4-one from the reaction system, a conventionally known method such as a solvent extraction method, a recrystallization method, or column chromatography can be appropriately adopted.
本発明により高収率でかつ高純度の７−アセトキシ−
6,7−ジヒドロ−3H,5H−シクロペンタ〔ｄ〕ピリミジン
−４−オン（Ｉ）を得ることができる。According to the present invention, high-yield and high-purity 7-acetoxy-
6,7-Dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one (I) can be obtained.
本発明の７−アセトキシ−6,7−ジヒドロ−3H,5H−シ
クロペンタ〔ｄ〕ピリミジン−４−オン（Ｉ）は下記の
方法によって、７−アセトキシ−４−クロロ−6,7−ジ
ヒドロ−5H−シクロペンタ〔ｄ〕ピリミジン（Ｘ）に誘
導される。The 7-acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one (I) of the present invention can be converted into 7-acetoxy-4-chloro-6,7-dihydro-5H by the following method. -Derived to cyclopenta [d] pyrimidine (X).
すなわち、クロル化剤としては、オキシ塩化リン、五
塩化リン、塩化チオニル等が用いられ、通常これらの使
用量は、７−アセトキシ−6,7−ジヒドロ−3H,5H−シク
ロペンタ〔ｄ〕ピリミジン−４−オンに対して1.0〜50
倍モル、好ましくは１〜20倍モルである。反応溶媒とし
ては反応に不活性なものであれば、特に限定されない
が、ジクロロメタン、クロロホルム、ジクロロエタン等
のハロゲン化炭化水素系溶媒、ベンゼン、トルエン、ヘ
キサン等の炭化水素系溶媒、エーテル、テトラヒドロフ
ラン、ジオキサン等のエーテル系溶媒等が使用できる。
また、クロル化剤自身を溶媒として用いることもでき
る。 That is, as the chlorinating agent, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride and the like are used, and the amount thereof is usually 7-acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidine- 1.0 to 50 for 4-on
The molar amount is double, preferably 1 to 20 times. The reaction solvent is not particularly limited as long as it is inert to the reaction, but is a halogenated hydrocarbon solvent such as dichloromethane, chloroform and dichloroethane, a hydrocarbon solvent such as benzene, toluene and hexane, ether, tetrahydrofuran and dioxane. And the like, such as ether solvents can be used.
Further, the chlorinating agent itself can be used as a solvent.
さらに反応促進剤として、トリエチルアミン、ピリジ
ン、N,N−ジエチルアニリン、４−ジメチルアミノピリ
ジン等のアミン類およびジメチルホルムアミド、ジメチ
ルアセトアミド等のアミド類の添加が推奨される。これ
らの促進剤は通常0.1〜20倍モル、好ましくは0.1〜５倍
モル使用される。Further, addition of amines such as triethylamine, pyridine, N, N-diethylaniline and 4-dimethylaminopyridine and amides such as dimethylformamide and dimethylacetamide are recommended as reaction accelerators. These accelerators are generally used in an amount of 0.1 to 20 times by mole, preferably 0.1 to 5 times by mole.
反応温度としては通常０°〜200℃で適宜選ばれる
が、好ましくは０°〜120℃である。The reaction temperature is usually selected in the range of 0 ° to 200 ° C, preferably 0 ° to 120 ° C.
反応は、条件によって異なるが、通常20時間以内に終
了する。反応終了後、７−アセトキシ−４−クロロ−6,
7−ジヒドロ−5H−シクロペンタ〔ｄ〕ピリミジンを反
応系から回収する方法としては、従来公知の方法、例え
ば溶媒抽出法、カラムクロマトグラフィーなど適宜採用
することにより行うことができる。The reaction depends on the conditions, but is usually completed within 20 hours. After completion of the reaction, 7-acetoxy-4-chloro-6,
As a method for recovering 7-dihydro-5H-cyclopenta [d] pyrimidine from the reaction system, a conventionally known method such as a solvent extraction method or column chromatography can be appropriately adopted.
以下本発明を実施例により具体的に説明するが本発明
はこれに限定されるものではない。Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.
〔実施例１〕 ７−メトキシ−6,7−ジヒドロ−3H,5H−シクロペンタ
〔ｄ〕ピリミジン−４−オン13.29gを無水酢酸40.8g中
に懸濁させ、次いで氷冷下で濃硫酸（97％）6.6mlをゆ
っくり滴下した。滴下終了後、室温で３時間撹拌し、更
に55℃で２時間撹拌した。反応液を冷却し、次いで、氷
冷下で濃アンモニア水を滴下して中和した。クロロホル
ムで抽出し得られたクロロホルム層を無水硫酸ナトリウ
ムで乾燥した。クロロホルムを減圧下で留去して、７−
アセトキシ−6,7−ジヒドロ−3H,5H−シクロペンタ
〔ｄ〕ピリミジン−４−オン12.34gを無色粉末状結晶と
して得た。Example 1 7.29 g of 7-methoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one was suspended in 40.8 g of acetic anhydride, and then concentrated sulfuric acid (97 %) 6.6 ml was slowly added dropwise. After completion of dropping, the mixture was stirred at room temperature for 3 hours and further at 55 ° C. for 2 hours. The reaction solution was cooled, and then concentrated ammonia water was added dropwise under ice cooling for neutralization. The chloroform layer obtained by extraction with chloroform was dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure to give 7-
Acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one (12.34 g) was obtained as colorless powdery crystals.
m.p.178-180℃ NMR（CDCl3，δppm）:1.93-2.10（m,1H）、2.14（s,3
H）、2.55-3.07（m,3H）、6.08（t,1H）、8.19（s,1
H）、12.87（br.1H） 〔実施例２〕 無水酢酸12.25g中に氷冷下で濃硫酸3.3mlを滴下し、
次いで７−メトキシ−6,7−ジヒドロ−3H,5H−シクロペ
ンタ〔ｄ〕ピリミジン−４−オン6.64gを添加した。得
られた混合物を室温で１時間、更に62℃で３時間撹拌し
た。得られた反応液を実施例１と同様に処理して、７−
アセトキシ−6,7−ジヒドロ−3H,5H−シクロペンタ
〔ｄ〕ピリミジン−４−オン5.69gを得た。mp178-180 ° C NMR (CDCl 3 , δppm): 1.93-2.10 (m, 1H), 2.14 (s, 3
H), 2.55-3.07 (m, 3H), 6.08 (t, 1H), 8.19 (s, 1
H), 12.87 (br.1H) [Example 2] 3.3 ml of concentrated sulfuric acid was added dropwise to 12.25 g of acetic anhydride under ice cooling,
Then 6.64 g of 7-methoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one was added. The resulting mixture was stirred at room temperature for 1 hour and then at 62 ° C. for 3 hours. The obtained reaction solution was treated in the same manner as in Example 1 to give 7-
Acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one (5.69 g) was obtained.
〔実施例３〕 無水酢酸12.25gに７−メトキシ−6,7−ジヒドロ−3H,
5H−シクロペンタ〔ｄ〕ピリミジン−４−オン6.65gお
よび40％三フッ化ホウ素・酢酸コンプレックス16.95gを
加えた後、75℃で２時間撹拌した。反応液を冷却後、氷
冷下で飽和炭酸ナトリウム水溶液を加えて中和した。ク
ロロホルムで抽出し、クロロホルム層を無水硫酸ナトリ
ウムで乾燥した。クロロホルムを減圧下で留去して、７
−アセトキシ−6,7−ジヒドロ−3H,5H−シクロペンタ
〔ｄ〕ピリミジン−４−オン5.17gを得た。Example 3 To 12.25 g of acetic anhydride was added 7-methoxy-6,7-dihydro-3H,
After adding 6.65 g of 5H-cyclopenta [d] pyrimidin-4-one and 16.95 g of 40% boron trifluoride / acetic acid complex, the mixture was stirred at 75 ° C for 2 hours. After cooling the reaction solution, it was neutralized by adding a saturated sodium carbonate aqueous solution under ice cooling. It was extracted with chloroform, and the chloroform layer was dried over anhydrous sodium sulfate. The chloroform was distilled off under reduced pressure to give 7
5.17 g of -acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one were obtained.
〔実施例４〕 無水酢酸12.25gに７−メトキシ−6,7−ジヒドロ−3H,
5H−シクロペンタ〔ｄ〕ピリミジン−４−オン6.65g、
酢酸ナトリウム0.66gおよび40％三フッ化ホウ素・酢酸
コンプレックス10.17gを加えた後、還流下で４時間反応
を行なった。得られた反応液を実施例３と同様に処理し
て、７−アセトキシ−6,7−ジヒドロ−3H,5H−シクロペ
ンタ〔ｄ〕ピリミジン−４−オン5.44gを得た。Example 4 To 12.25 g of acetic anhydride was added 7-methoxy-6,7-dihydro-3H,
5H-cyclopenta [d] pyrimidin-4-one 6.65 g,
After adding 0.66 g of sodium acetate and 10.17 g of 40% boron trifluoride / acetic acid complex, the mixture was reacted under reflux for 4 hours. The obtained reaction liquid was treated in the same manner as in Example 3 to obtain 5.44 g of 7-acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one.
〔実施例５〕 無水酢酸6.13gに７−メトキシ−6,7−ジヒドロ−3H,5
H−シクロペンタ〔ｄ〕ピリミジン−４−オン3.32gおよ
び三フッ化ホウ素・エーテル コンプレックス7.10gを
加えた後、75℃で１時間反応を行なった。得られた反応
液を実施例３と同様に処理して、７−アセトキシ−6,7
−ジヒドロ−3H,5H−シクロペンタ〔ｄ〕ピリミジン−
４−オン1.93gを得た。[Example 5] 7-methoxy-6,7-dihydro-3H, 5 was added to 6.13 g of acetic anhydride.
After adding 3.32 g of H-cyclopenta [d] pyrimidin-4-one and 7.10 g of boron trifluoride / ether complex, reaction was carried out at 75 ° C. for 1 hour. The obtained reaction solution was treated in the same manner as in Example 3 to give 7-acetoxy-6,7.
-Dihydro-3H, 5H-cyclopenta [d] pyrimidine-
Obtained 1.93 g of 4-one.
〔実施例６〕 無水酢酸12.25gに７−メトキシ−6,7−ジヒドロ−3H,
5H−シクロペンタ〔ｄ〕ピリミジン−４−オン3.32gお
よび塩化亜鉛2.73gを加えた後、95℃で７時間反応を行
った。反応終了後、反応液を高速液体クロマトグラフィ
ーにより分析＊した結果、７−アセトキシ−6,7−ジヒ
ドロ−3H,5H−シクロペンタ〔ｄ〕ピリミジン−４−オ
ン1.38gが生成していた。Example 6 To 12.25 g of acetic anhydride was added 7-methoxy-6,7-dihydro-3H,
After adding 3.32 g of 5H-cyclopenta [d] pyrimidin-4-one and 2.73 g of zinc chloride, reaction was carried out at 95 ° C for 7 hours. After the reaction was completed, the reaction solution was analyzed * by high performance liquid chromatography, and as a result, 1.38 g of 7-acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one was formed.
＊HPLC分析条件 カラム：（株）山村化学研究所充てんカラム YMC-pack A-303（ODs） カラム温度:40℃ 移動相:0.12％酢酸アンモニウム・アセトニトリル混液
（9:1） 流 量:0.8ml/min 保持時間:15.8min 〔実施例７〕 酸化ホウ素4.2g、７−メトキシ−6,7−ジヒドロ−3H,
5H−シクロペンタ〔ｄ〕ピリミジン−４−オン10.0g
に、無水酢酸30.6g及び無水トリフルオロ酢酸37.8gを加
え、80℃で５時間反応を行なった。反応終了後、反応液
を有速液体クロマトグラフィーにより分析した結果、７
−アセトキシ−6,7−ジヒドロ−3H,5H−シクロペンタ
〔ｄ〕ピリミジン−４−オン7.0gが生成していた。* HPLC analysis conditions Column: Yamamura Chemical Laboratory packed column YMC-pack A-303 (ODs) Column temperature: 40 ° C Mobile phase: 0.12% ammonium acetate / acetonitrile mixed solution (9: 1) Flow rate: 0.8 ml / min Holding time: 15.8 min [Example 7] Boron oxide 4.2 g, 7-methoxy-6,7-dihydro-3H,
5H-cyclopenta [d] pyrimidin-4-one 10.0 g
To this, 30.6 g of acetic anhydride and 37.8 g of trifluoroacetic anhydride were added, and the reaction was carried out at 80 ° C. for 5 hours. After the reaction was completed, the reaction solution was analyzed by speed-performance liquid chromatography.
7.0 g of -acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one had formed.
〔実施例８〕 ７−メトキシ−6,7−ジヒドロ−3H,5H−シクロペンタ
〔ｄ〕ピリミジン−４−オン6.0gに、無水酢酸55.2g及
び無水トリフルオロ酢酸75.5gを加え、室温にて攪拌し
ながらホウ酸6.6gを３回に分けて添加した。さらに２時
間攪拌した後に、実施例１と同様の後処理を行ない、７
−アセトキシ−6,7−ジヒドロ−3H,5H−シクロペンタ
〔ｄ〕ピリミジン−４−オン4.9gを得た。[Example 8] To 6.0 g of 7-methoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one, 55.2 g of acetic anhydride and 75.5 g of trifluoroacetic anhydride were added and stirred at room temperature. While adding 6.6 g of boric acid in three portions. After stirring for another 2 hours, the same post-treatment as in Example 1 was performed, and
4.9 g of -acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one were obtained.
上記のようにして得られた７−アセトキシ−6,7−ジ
ヒドロ−3H,5H−シクロペンタ〔ｄ〕ピリミジン−４−
オンは、以下に参考例として示す方法によって、４−
（４−シアノアニリノ）−6,7−ジヒドロ−７−ヒドロ
キシ−5H−シクロペンタ〔ｄ〕ピリミジンに誘導され
た。7-acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidine-4-obtained as described above
ON is performed by the method shown below as a reference example.
Derived to (4-cyanoanilino) -6,7-dihydro-7-hydroxy-5H-cyclopenta [d] pyrimidine.
（工程１）７−アセトキシ−４−クロロ−6,7−ジヒド
ロ−5H−シクロペンタ〔ｄ〕ピリミジンの合成 ７−アセトキシ−6,7−ジヒドロ−3H,5H−シクロペン
タ〔ｄ〕ピリミジン−４−オン38.0gをジクロルエタン1
00mlとトルエン100mlの混合液に懸濁させた。室温でオ
キシ塩化リン19.2mlを加え、次いでトリエチルアミン2
7.3mlを滴下した。滴下終了後、加熱し、還流下で２時
間反応させた。反応後、トルエン200mlを加えた後、有
機層を氷水30mlで２回洗浄した。得られた有機層を無水
硫酸ナトリウムで乾燥した後、減圧下で溶媒を除去し
て、７−アセトキシ−４−クロロ−6,7−ジヒドロ−5H
−シクロペンタ〔ｄ〕ピリミジン40.5gを無色油状物と
して得た。(Step 1) Synthesis of 7-acetoxy-4-chloro-6,7-dihydro-5H-cyclopenta [d] pyrimidine 7-acetoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one 38.0 g of dichloroethane 1
It was suspended in a mixed solution of 00 ml and 100 ml of toluene. At room temperature, add 19.2 ml of phosphorus oxychloride, then triethylamine 2
7.3 ml was added dropwise. After completion of the dropping, the mixture was heated and reacted under reflux for 2 hours. After the reaction, 200 ml of toluene was added, and the organic layer was washed twice with 30 ml of ice water. The obtained organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 7-acetoxy-4-chloro-6,7-dihydro-5H.
40.5 g of cyclopenta [d] pyrimidine were obtained as colorless oil.
（工程２）７−アセトキシ−４−（４−シアノアニリ
ノ）−6,7−ジヒドロ−5H−シクロペンタ〔ｄ〕ピリミ
ジンの合成 （工程１）で得られた７−アセトキシ−４−クロロ−
6,7−ジヒドロ−5H−シクロペンタ〔ｄ〕ピリミジン39.
3g（0.185モル）及びｐ−アミノベンゾニトリル24g（0.
2モル）のエタノール180ml溶液を1.5時間加熱還流し
た。エタノールを減圧下に留去し、残渣をエタノール−
トルエンの1:1溶液で洗浄し、灰色結晶の７−アセトキ
シ−４−（４−シアノアニリノ）−6,7−ジヒドロ−5H
−シクロペンタ〔ｄ〕ピリミジン30gを得た。(Step 2) Synthesis of 7-acetoxy-4- (4-cyanoanilino) -6,7-dihydro-5H-cyclopenta [d] pyrimidine 7-acetoxy-4-chloro-obtained in (Step 1)
6,7-Dihydro-5H-cyclopenta [d] pyrimidine 39.
3 g (0.185 mol) and p-aminobenzonitrile 24 g (0.
A 180 ml solution of 2 mol of ethanol was heated under reflux for 1.5 hours. Ethanol was distilled off under reduced pressure, and the residue was ethanol-
It was washed with a 1: 1 solution of toluene to give 7-acetoxy-4- (4-cyanoanilino) -6,7-dihydro-5H as gray crystals.
30 g of cyclopenta [d] pyrimidine are obtained.
融点215〜217℃ マススペクトル,m/e:294（M+）,251,234 （工程３）４−（４−シアノアニリノ）−6,7−ジヒド
ロ−７−ヒドロキシ−5H−シクロペンタ〔ｄ〕ピリミジ
ンの合成 （工程２）で得られた７−アセトキシ−４−（４−シ
アノアニリノ）−6,7−ジヒドロ−5H−シクロペンタ
〔ｄ〕ピリミジン2.9g（0.01モル）をエタノール800ml
に溶解し、これに炭酸カリウム13.8g（0.1モル）の水溶
液160mlを加え、室温で一夜攪拌した。反応後溶媒を留
去し、残渣を水で洗浄した後、得られた結晶をエタノー
ルから再結晶して、４−（４−シアノアニリノ）−6,7
−ジヒドロ−７−ヒドロキシ−5H−シクロペンタ〔ｄ〕
ピリミジン（無色砂状結晶、mp.260-262℃（分解））1.
4gを得た。Melting point 215-217 ° C Mass spectrum, m / e: 294 (M + ), 251,234 (Step 3) Synthesis of 4- (4-cyanoanilino) -6,7-dihydro-7-hydroxy-5H-cyclopenta [d] pyrimidine 2.9 g (0.01 mol) of 7-acetoxy-4- (4-cyanoanilino) -6,7-dihydro-5H-cyclopenta [d] pyrimidine obtained in (Step 2) was added to 800 ml of ethanol.
Was dissolved in water, 160 ml of an aqueous solution of 13.8 g (0.1 mol) of potassium carbonate was added, and the mixture was stirred overnight at room temperature. After the reaction, the solvent was distilled off, the residue was washed with water, and the obtained crystals were recrystallized from ethanol to give 4- (4-cyanoanilino) -6,7.
-Dihydro-7-hydroxy-5H-cyclopenta [d]
Pyrimidine (colorless sand crystals, mp.260-262 ℃ (decomposition)) 1.
4 g were obtained.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 小田 広行 山口県宇部市大字小串1978番地の５ 宇 部興産株式会社宇部研究所内 (72)発明者 岩田 宜芳 東京都品川区広町１丁目２番58番地 三 共株式会社内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Hiroyuki Oda Inventor Hiroyuki Oda, Ube City, Ube City, Yamaguchi Prefecture 5 1978, Ube Laboratory Ltd. (72) Inventor Yoshiyoshi Iwata 1-2-2 Hiromachi, Shinagawa-ku, Tokyo Address 58 Sankyo Co., Ltd.
Claims (2)
シクロペンタ〔ｄ〕ピリミジン−４−オン。1. 1-Acetoxy-6,7-dihydro-3H, 5H-
Cyclopenta [d] pyrimidin-4-one.
クロペンタ〔ｄ〕ピリミジン−４−オンを酸の存在下
で、無水酢酸と反応させることを特徴とする７−アセト
キシ−6,7−ジヒドロ−3H,5H−シクロペンタ〔ｄ〕ピリ
ミジン−４−オンの製法。2. A 7-acetoxy-6 characterized in that 7-methoxy-6,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one is reacted with acetic anhydride in the presence of an acid. Process for producing 7,7-dihydro-3H, 5H-cyclopenta [d] pyrimidin-4-one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11648389A JP2685896B2 (en) | 1989-05-10 | 1989-05-10 | Cyclopenta [d] pyrimidine derivative and process for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11648389A JP2685896B2 (en) | 1989-05-10 | 1989-05-10 | Cyclopenta [d] pyrimidine derivative and process for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02295980A JPH02295980A (en) | 1990-12-06 |
| JP2685896B2 true JP2685896B2 (en) | 1997-12-03 |
Family
ID=14688231
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11648389A Expired - Fee Related JP2685896B2 (en) | 1989-05-10 | 1989-05-10 | Cyclopenta [d] pyrimidine derivative and process for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2685896B2 (en) |
-
1989
- 1989-05-10 JP JP11648389A patent/JP2685896B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02295980A (en) | 1990-12-06 |
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