JP4449211B2 - 6- (1-fluoroethyl) -5-iodo-4-pyrimidone and process for producing the same - Google Patents

6- (1-fluoroethyl) -5-iodo-4-pyrimidone and process for producing the same Download PDF

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JP4449211B2
JP4449211B2 JP2000384776A JP2000384776A JP4449211B2 JP 4449211 B2 JP4449211 B2 JP 4449211B2 JP 2000384776 A JP2000384776 A JP 2000384776A JP 2000384776 A JP2000384776 A JP 2000384776A JP 4449211 B2 JP4449211 B2 JP 4449211B2
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Prior art keywords
fluoroethyl
pyrimidone
iodo
formula
compound
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JP2002187883A (en
Inventor
勝利 藤井
庄司 敷田
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Ube Corp
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Ube Industries Ltd
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Description

【0001】
【発明の属する技術分野】
本発明は、医薬・農薬、例えば、殺虫剤・殺ダニ剤・殺菌剤などとして有用なアミノピリミジン誘導体(特開平11−302261号公報)の合成中間体として4−クロル−6−(1−フルオロエチル)−5−ヨードピリミジンが用いられている。
この4−クロル−6−(1−フルオロエチル)−5−ヨードピリミジンを製造するのに有用である新規な6−(1−フルオロエチル)−5−ヨード−4−ピリミドンに関するものである。
【0002】
【従来の技術】
前記特開平11−302261号公報の化合物製造に於いて使用される4−クロル−6−(1−フルオロエチル)−5−ヨードピリミジンは幾つか知られている(例えば、特願平10−102414号公報)。
しかしながら、この方法は
次式:
【0003】
【化4】

Figure 0004449211
【0004】
に示す様に製造工程が長く、しかも収率が悪いことから工業的な方法とは言いがたい。
また、本発明の6−(1−フルオロエチル)−5−ヨード−4−ピリミドンから4−クロル−6−(1−フルオロエチル)−5−ヨードピリミジンを製造する方法の開示も認められない。
【0005】
【発明が解決しようとする課題】
本発明の課題は、医薬・農薬の中間体などとして有用な新規な6−(1−フルオロエチル)−5−ヨード−4−ピリミドンを提供することである。
【0006】
【課題を解決するための手段】
本発明者らは、前記の課題を解決するために検討した結果、新規な6−(1−フルオロエチル)−5−ヨード−4−ピリミドンが前記アミノピリミジン誘導体の重要な中間体である4−クロル−6−(1−フルオロエチル)−5−ヨードピリミジンの原料となることを見い出し、さらにその製法を確立して、本発明を完成した。
即ち、本発明は次の通りである。
第1の発明は、次式(1):
【0007】
【化5】
Figure 0004449211
【0008】
(式中、*は不斉炭素原子を表す。)
で示される6−(1−フルオロエチル)−5−ヨード−4−ピリミドンに関するものである。
第2の発明は
次式(2):
【0009】
【化6】
Figure 0004449211
【0010】
(式中、*は前記と同義である。)
で示される6−(1−フルオロエチル)−4−ピリミドンと
次式(3):
【0011】
【化7】
Figure 0004449211
【0012】
(式中、Xは塩素原子又は臭素原子を表す。)
で示されるハロゲン化ヨウ素類とを反応させることを特徴とする請求項1記載の式(1)に記載6−(1−フルオロエチル)−5−ヨード−4−ピリミドンの製法。
【0013】
【発明の実施の形態】
以下、本発明について詳細に説明する。
前記の化合物(3)で表した置換基は、次の通りである。
Xにおけるハロゲン原子としては塩素原子,臭素原子を挙げることができるが;塩素原子が好ましい。
本発明の化合物(1)は*で示した不斉炭素原子を含むので、これらに由来する個々の光学異性体、ラセミ体、又はそれらの混合物のいずれも本発明に含まれる。
【0014】
本発明の化合物(1)の合成法を、さらに詳細に述べる。
合成法は、化合物(2)と化合物(3)とを、溶媒中で反応させて化合物(1)を得る方法である。
【0015】
溶媒の種類としては、本反応に直接関与しないものであれば特に限定されず、例えば、ベンゼン、トルエン、キシレン、メチルナフタリン、石油エーテル、リグロイン、ヘキサン、クロルベンゼン、ジクロルベンゼン、クロロホルム、ジクロルメタン、ジクロルエタン、トリクロルエチレンのような塩素化された又はされていない芳香族、脂肪族、脂環式の炭化水素類;テトラヒドロフラン、シオキサン、ジエチルエーテルなどのようなエーテル類;酢酸、プロピオン酸など脂肪族カルボン酸;及び前記溶媒の混合物などを挙げることができるが;酢酸など脂肪族カルボン酸が好ましい。
【0016】
溶媒の使用量は、化合物(2)が5〜80重量%になるようにして使用することができるが;10〜70重量%が好ましい。
反応温度は、特に限定されないが、室温から使用する溶媒の沸点以下の温度範囲内であり;10〜30℃が好ましい。
反応時間は、前記の濃度、温度によって変化するが;通常2〜8時間である。
原料化合物の使用量は、化合物(2)に対して化合物(3)が、1.0〜3倍モルであるが;1〜1.1倍モルが好ましい。
本発明で用いる化合物(2)は、例えば、特開平11−255752号公報に記載の方法に準じて、次式に示す方法で製造できる。
【0017】
【化8】
Figure 0004449211
【0018】
本発明で用いる化合物(3)は、例えば、Org.Syn.Coll.Vol.,2,196(1953)に記載の方法に準じて、次式に示す方法で製造できる。
【0019】
【化9】
Figure 0004449211
【0020】
(式中、Xは塩素原子又は臭素原子を表す。)
以上のようにして製造された目的の化合物(1)は、反応終了後、抽出、濃縮、ロ過などの通常の後処理を行い、必要に応じて蒸留、再結晶、各種クロマトグラフィーなどの公知の手段で適宣精製することができる。
【0021】
本発明の化合物(1)は次式に示すように容易に4−クロロ−6−(1−フルオロエチル)−5−ヨードピリミジンを合成することができる。
【0022】
【化10】
Figure 0004449211
【0023】
【実施例】
以下、本発明を実施例、参考例及び比較例によって具体的に説明する。なお、これらは、本発明の範囲を限定するものではない。
【0024】
実施例〔化合物(1)の合成法〕
6−(1−フルオロエチル)−5−ヨード−4−ピリミドンの合成
ヨード(50.8g)を酢酸(500ml)に加え、室温撹拌下に塩素(15g)を吹き込み調製した1塩化ヨウ素の酢酸溶液を、6−(1−フルオロエチル)−4−ピリミドン(56.8g)の酢酸(150ml)溶液に室温撹拌下に滴下し、6時間撹拌した。
反応終了後、減圧下に酢酸を留去し、水(300ml)を加え溶解し、2N水酸化ナトリウム及び飽和炭酸水素ナトリウム水溶液でpH5に調整する。析出した結晶を濾集し、水洗、乾燥し、淡黄土色結晶の目的物85gを得た。
更に、酢酸エチル−ヘキサンによる再結晶で精製することによって、無色小針状結晶である目的化合物を76.0g得た。
【0025】
m.p.195〜196℃
1H−NMR(CDCl3,δppm)
1.61〜1.71(3H,d−t)、5.81〜5.97(1H,d−q)
8.29(1H,s)、13.0(1H,bs)
【0026】
参考例1〔化合物(2)の合成法〕
6−(1−フルオロエチル)−4−ピリミドンの合成
4−フルオロ−3−オキソペンタン酸メチルエステル(93.3g)をメタノール(1000ml)に溶解し、28%ナトリウムメチラート/メタノール溶液(365g)とホルムアミジン酢酸塩(98.4g)を順次加え、40℃で12時間加熱還流した。
反応終了後、10℃以下に冷却し、濃硫酸(95.1g)と水(85g)の混合液を添加した。次いで、50℃で30分撹拌し、不溶物を濾別し、濾液を減圧下に濃縮した。得られた残渣をイソプロパノールで再結晶することによって、無色結晶である目的化合物を58g得た。
m.p.170.0〜171.5℃
【0027】
参考例2〔化合物(10)の合成法〕
4−クロロ−6−(1−フルオロエチル)−5−ヨードピリミジンの合成
6−(1−フルオロエチル)−5−ヨード−4−ピリミドン(53.6g)を酢酸エチル(180ml)に加え、N,N−ジメチルフォルムアミド(1.5g)を添加し、70℃に加温撹拌する。次いで、チオニルクロライド(28.6g)を滴下し、3時間撹拌して反応を完結した。
反応混合物冷却後、氷冷水に加え、2N水酸化ナトリウムでpH4に調整し、酢酸エチル層を分取し、水洗、無水硫酸ナトリウムで乾燥した。次いで、減圧下溶媒を留去し、得られた残渣を減圧蒸留で精製することによって、淡黄色液体である目的物を54.6g得た。
【0028】
b.p.116〜118℃/4mmHg
1H−NMR(CDCl3,δppm)
1.63〜1.77(3H,d−d)、5.88〜6.08(1H,d−q)
8.70(1H,s)
【0029】
比較例(特願平10−102414号公報による4−クロロ−6−(1−フルオロエチル)−5−ヨードピリミジンの合成)
(1)6−エチル−5−ヨード−4−ピリミドンの合成
ヨード(50.8g)を酢酸(700ml)に加え、塩素(15g)を吹き込んだ溶液に、6−エチル−4−ピリミドン(50g)の酢酸(150ml)溶液を滴下し、4時間撹拌した。
反応終了後、減圧下に酢酸を留去し、得られた結晶を酢酸エチルによる再結晶で精製することによって、無色結晶である目的化合物を24.8g得た。
【0030】
(2)4−クロロ−6−エチル−5−ヨードピリミジンの合成
6−エチル−5−ヨード−4−ピリミドン(10g)にオキシ塩化リン(40g)を加え、4時間加熱還流した。
反応終了後、過剰のオキシ塩化リンを減圧下に留去し、得られた残渣を氷水中に注加し、トルエンで目的化合物を抽出した。抽出液を水洗し、無水硫酸ナトリウムで乾燥した後に溶媒を減圧下で留去した。
得られた油状物をシリカゲルカラム(ワコーゲルC−200,トルエン:酢酸エチル=10:1溶出)で精製することによって、淡黄色結晶である目的化合物を9.3g得た。
【0031】
(3)4−クロロ−6−(1−クロロエチル)−5−ヨードピリミジンの合成
4−クロロ−6−エチル−5−ヨードピリミジン(5g)をクロロフォルム(100ml)に溶解し、室温撹拌下に塩素ガスを吹き込んだ。
反応終了後、窒素ガスを吹き込み過剰の塩素ガスを除去後、減圧下に溶媒を留去した。
得られた油状物をシリカゲルカラム(ワコーゲルC−200,トルエン:酢酸エチル=20:1溶出)で精製することによって、淡黄色油状液体である目的化合物を3.4g得た。
【0032】
(4)6−(1−アセトキシエチル)−4−クロロ−5−ヨードピリミジン(化合物4)の合成
4−クロロ−6−(1−クロロエチル)−5−ヨードピリミジン(3.6g)をN,N−ジメチルホルムアミド(70ml)に溶解し、酢酸カリウム(2.4g)と炭酸カリウム(0.7g)を加え、約60℃で4時間加熱撹拌した。
反応終了後、反応混合物に水を加え、分離する油状物をトルエンで抽出し、水洗後、無水硫酸ナトリウムで乾燥した。次いで、減圧下に溶媒を留去し、得られた残渣をカラムクロマトグラフィー(ワコーゲルC−200、トルエン:酢酸エチル=10:1溶出)で精製することによって、無色結晶である目的物を1.0g得た。
【0033】
(5)4−クロロ−6−(1−ヒドロキシエチル)−5−ヨードピリミジンの合成
4−クロロ−6−(1−アセトキシエチル)−5−ヨードピリミジン(1.0g)をエタノール(20ml)に溶解し、撹拌下に1N−水酸化ナトリウム水溶液(20ml)を滴下した。滴下後、更に1時間室温で撹拌し、反応を完結した。次いで、減圧下溶媒を留去し、酢酸エチルで目的化合物を抽出し、水洗、無水硫酸ナトリウムで乾燥した後に溶媒を減圧下留去した。
得られた残渣をカラムクロマトグラフィー(ワコーゲルC−200、トルエン:酢酸エチル=20:1溶出)で精製することによって、淡黄色油状液体である目的物を0.5g得た。
【0034】
(6)4−クロロ−6−(1−フルオロエチル)−5−ヨードピリミジンの合成
5−クロロ−6−(1−ヒドロキシエチル)−4−(2−(4−ヒドロキシフェニル)エチルアミノ)ピリミジン(0.5g)をジクロロメタン(20ml)に溶解し、氷冷、撹拌下にジエチルアミノサルファートリフルオライド(0.3g)を滴下し、さらに1時間室温で撹拌して反応を完結した。
反応混合物に冷水を加え、ジクロロメタン層を分取し、水洗、無水硫酸ナトリウムで乾燥した。次いで、減圧下溶媒を留去し、得られた残渣をカラムクロマトグラフィー(ワコーゲルC−200、クロロホルム溶出)で精製することによって、淡黄色液体である目的物を0.4g得た。
【0035】
【発明の効果】
本発明の新規な6−(1−フルオロエチル)−5−ヨード−4−ピリミドンは、医薬・農薬などの中間体として有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention provides 4-chloro-6- (1-fluoro) as a synthetic intermediate of aminopyrimidine derivatives (Japanese Patent Laid-Open No. 11-302261) useful as pharmaceuticals and agricultural chemicals, for example, insecticides, acaricides, fungicides and the like. Ethyl) -5-iodopyrimidine is used.
The present invention relates to a novel 6- (1-fluoroethyl) -5-iodo-4-pyrimidone which is useful for producing 4-chloro-6- (1-fluoroethyl) -5-iodopyrimidine.
[0002]
[Prior art]
Several 4-chloro-6- (1-fluoroethyl) -5-iodopyrimidines used in the production of compounds described in JP-A-11-302261 are known (for example, Japanese Patent Application No. 10-102414). Issue gazette).
However, this method has the following formula:
[0003]
[Formula 4]
Figure 0004449211
[0004]
Therefore, it is difficult to say that it is an industrial method because the production process is long and the yield is poor.
Also, there is no disclosure of a method for producing 4-chloro-6- (1-fluoroethyl) -5-iodopyrimidine from 6- (1-fluoroethyl) -5-iodo-4-pyrimidone of the present invention.
[0005]
[Problems to be solved by the invention]
An object of the present invention is to provide a novel 6- (1-fluoroethyl) -5-iodo-4-pyrimidone useful as an intermediate for pharmaceuticals and agricultural chemicals.
[0006]
[Means for Solving the Problems]
As a result of investigations to solve the above problems, the present inventors have found that novel 6- (1-fluoroethyl) -5-iodo-4-pyrimidone is an important intermediate of the aminopyrimidine derivative 4- It was found that it was a raw material for chloro-6- (1-fluoroethyl) -5-iodopyrimidine, and its production method was established to complete the present invention.
That is, the present invention is as follows.
The first invention is the following formula (1):
[0007]
[Chemical formula 5]
Figure 0004449211
[0008]
(In the formula, * represents an asymmetric carbon atom.)
6- (1-fluoroethyl) -5-iodo-4-pyrimidone
The second invention is the following formula (2):
[0009]
[Chemical 6]
Figure 0004449211
[0010]
(In the formula, * is as defined above.)
6- (1-fluoroethyl) -4-pyrimidone represented by the following formula (3):
[0011]
[Chemical 7]
Figure 0004449211
[0012]
(In the formula, X represents a chlorine atom or a bromine atom.)
A process for producing 6- (1-fluoroethyl) -5-iodo-4-pyrimidone according to formula (1) according to claim 1, characterized in that it is reacted with an iodine halide represented by formula (1).
[0013]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
The substituents represented by the compound (3) are as follows.
Examples of the halogen atom in X include a chlorine atom and a bromine atom; a chlorine atom is preferred.
Since the compound (1) of the present invention contains an asymmetric carbon atom indicated by *, any of the individual optical isomers, racemates or mixtures thereof derived from these is also included in the present invention.
[0014]
The synthesis method of the compound (1) of the present invention will be described in more detail.
The synthesis method is a method in which compound (2) and compound (3) are reacted in a solvent to obtain compound (1).
[0015]
The type of the solvent is not particularly limited as long as it does not directly participate in this reaction. For example, benzene, toluene, xylene, methylnaphthalene, petroleum ether, ligroin, hexane, chlorobenzene, dichlorobenzene, chloroform, dichloromethane, Chlorinated or non-chlorinated aromatic, aliphatic, and alicyclic hydrocarbons such as dichloroethane and trichloroethylene; Ethers such as tetrahydrofuran, thioxane, and diethyl ether; Aliphatic carboxyl such as acetic acid and propionic acid And a mixture of the above-mentioned solvents, and aliphatic carboxylic acids such as acetic acid are preferred.
[0016]
The amount of the solvent used can be such that the compound (2) is 5 to 80% by weight; however, it is preferably 10 to 70% by weight.
Although reaction temperature is not specifically limited, It exists in the temperature range below the boiling point of the solvent to be used from room temperature; 10-30 degreeC is preferable.
The reaction time varies depending on the concentration and temperature; however, it is usually 2 to 8 hours.
The amount of the raw material compound used is 1.0 to 3 times mol of the compound (3) with respect to the compound (2);
The compound (2) used in the present invention can be produced, for example, by the method shown in the following formula according to the method described in JP-A-11-255752.
[0017]
[Chemical 8]
Figure 0004449211
[0018]
The compound (3) used in the present invention is, for example, Org. Syn. Coll. Vol. , 2, 196 (1953).
[0019]
[Chemical 9]
Figure 0004449211
[0020]
(In the formula, X represents a chlorine atom or a bromine atom.)
The target compound (1) produced as described above is subjected to usual post-treatments such as extraction, concentration and filtration after completion of the reaction, and publicly known methods such as distillation, recrystallization and various chromatography as necessary. It can be properly purified by means of
[0021]
Compound (1) of the present invention can easily synthesize 4-chloro-6- (1-fluoroethyl) -5-iodopyrimidine as shown in the following formula.
[0022]
[Chemical Formula 10]
Figure 0004449211
[0023]
【Example】
Hereinafter, the present invention will be specifically described with reference to Examples, Reference Examples and Comparative Examples. These do not limit the scope of the present invention.
[0024]
Example [Synthesis Method of Compound (1)]
Synthesis of 6- (1-fluoroethyl) -5-iodo-4-pyrimidone Iodine chloride (50.8 g) was added to acetic acid (500 ml) and chlorine (15 g) was blown into the mixture with stirring at room temperature. Was added dropwise to a solution of 6- (1-fluoroethyl) -4-pyrimidone (56.8 g) in acetic acid (150 ml) with stirring at room temperature, and stirred for 6 hours.
After completion of the reaction, acetic acid is distilled off under reduced pressure, water (300 ml) is added and dissolved, and the pH is adjusted to 5 with 2N sodium hydroxide and saturated aqueous sodium hydrogen carbonate solution. The precipitated crystals were collected by filtration, washed with water and dried to obtain 85 g of the desired product as pale ocher crystals.
Further, purification by recrystallization with ethyl acetate-hexane gave 76.0 g of the target compound as colorless small needle crystals.
[0025]
m. p. 195-196 ° C
1 H-NMR (CDCl 3 , δ ppm)
1.61-1.71 (3H, dt), 5.81-5.97 (1H, dq)
8.29 (1H, s), 13.0 (1H, bs)
[0026]
Reference Example 1 [Synthesis Method of Compound (2)]
Synthesis of 6- (1-fluoroethyl) -4-pyrimidone 4-fluoro-3-oxopentanoic acid methyl ester (93.3 g) was dissolved in methanol (1000 ml), and 28% sodium methylate / methanol solution (365 g) And formamidine acetate (98.4 g) were sequentially added, and the mixture was heated to reflux at 40 ° C. for 12 hours.
After completion of the reaction, the mixture was cooled to 10 ° C. or lower, and a mixed solution of concentrated sulfuric acid (95.1 g) and water (85 g) was added. Subsequently, the mixture was stirred at 50 ° C. for 30 minutes, insoluble matters were filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was recrystallized from isopropanol to obtain 58 g of the objective compound as colorless crystals.
m. p. 170.0-171.5 ° C
[0027]
Reference Example 2 [Synthesis Method of Compound (10)]
Synthesis of 4-chloro-6- (1-fluoroethyl) -5-iodopyrimidine 6- (1-fluoroethyl) -5-iodo-4-pyrimidone (53.6 g) was added to ethyl acetate (180 ml) and N , N-dimethylformamide (1.5 g) is added, and the mixture is heated to 70 ° C. with stirring. Subsequently, thionyl chloride (28.6 g) was added dropwise and stirred for 3 hours to complete the reaction.
After cooling the reaction mixture, it was added to ice-cold water, adjusted to pH 4 with 2N sodium hydroxide, the ethyl acetate layer was separated, washed with water, and dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled off under reduced pressure, and the obtained residue was purified by distillation under reduced pressure to obtain 54.6 g of the desired product as a pale yellow liquid.
[0028]
b. p. 116-118 ° C / 4mmHg
1 H-NMR (CDCl 3 , δ ppm)
1.63-1.77 (3H, dd), 5.88-6.08 (1H, dq)
8.70 (1H, s)
[0029]
Comparative Example (Synthesis of 4-chloro-6- (1-fluoroethyl) -5-iodopyrimidine according to Japanese Patent Application No. 10-102414)
(1) Synthesis of 6-ethyl-5-iodo-4-pyrimidone Iodo (50.8 g) was added to acetic acid (700 ml), and chlorine (15 g) was bubbled into the solution, 6-ethyl-4-pyrimidone (50 g). Of acetic acid (150 ml) was added dropwise and stirred for 4 hours.
After completion of the reaction, acetic acid was distilled off under reduced pressure, and the resulting crystals were purified by recrystallization with ethyl acetate to obtain 24.8 g of the target compound as colorless crystals.
[0030]
(2) Synthesis of 4-chloro-6-ethyl-5-iodopyrimidine Phosphorus oxychloride (40 g) was added to 6-ethyl-5-iodo-4-pyrimidone (10 g), and the mixture was heated to reflux for 4 hours.
After completion of the reaction, excess phosphorus oxychloride was distilled off under reduced pressure, the resulting residue was poured into ice water, and the target compound was extracted with toluene. The extract was washed with water and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.
The obtained oil was purified with a silica gel column (Wakogel C-200, elution with toluene: ethyl acetate = 10: 1) to obtain 9.3 g of the target compound as pale yellow crystals.
[0031]
(3) Synthesis of 4-chloro-6- (1-chloroethyl) -5-iodopyrimidine 4-chloro-6-ethyl-5-iodopyrimidine (5 g) was dissolved in chloroform (100 ml) and chlorine was stirred at room temperature. Gas was blown in.
After completion of the reaction, nitrogen gas was blown in to remove excess chlorine gas, and then the solvent was distilled off under reduced pressure.
The obtained oil was purified with a silica gel column (Wakogel C-200, elution with toluene: ethyl acetate = 20: 1) to obtain 3.4 g of the target compound as a pale yellow oily liquid.
[0032]
(4) Synthesis of 6- (1-acetoxyethyl) -4-chloro-5-iodopyrimidine (Compound 4) 4-chloro-6- (1-chloroethyl) -5-iodopyrimidine (3.6 g) was converted to N, The mixture was dissolved in N-dimethylformamide (70 ml), potassium acetate (2.4 g) and potassium carbonate (0.7 g) were added, and the mixture was heated with stirring at about 60 ° C. for 4 hours.
After completion of the reaction, water was added to the reaction mixture, and the separated oil was extracted with toluene, washed with water, and dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (Wakogel C-200, elution with toluene: ethyl acetate = 10: 1). 0 g was obtained.
[0033]
(5) Synthesis of 4-chloro-6- (1-hydroxyethyl) -5-iodopyrimidine 4-chloro-6- (1-acetoxyethyl) -5-iodopyrimidine (1.0 g) in ethanol (20 ml) It melt | dissolved and 1N-sodium hydroxide aqueous solution (20 ml) was dripped under stirring. After the dropwise addition, the reaction was completed by further stirring for 1 hour at room temperature. Subsequently, the solvent was distilled off under reduced pressure, the target compound was extracted with ethyl acetate, washed with water and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.
The obtained residue was purified by column chromatography (Wakogel C-200, elution with toluene: ethyl acetate = 20: 1) to obtain 0.5 g of the desired product as a pale yellow oily liquid.
[0034]
(6) Synthesis of 4-chloro-6- (1-fluoroethyl) -5-iodopyrimidine 5-chloro-6- (1-hydroxyethyl) -4- (2- (4-hydroxyphenyl) ethylamino) pyrimidine (0.5 g) was dissolved in dichloromethane (20 ml), and diethylaminosulfur trifluoride (0.3 g) was added dropwise under ice-cooling and stirring, and the mixture was further stirred at room temperature for 1 hour to complete the reaction.
Cold water was added to the reaction mixture, and the dichloromethane layer was separated, washed with water, and dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (Wakogel C-200, eluted with chloroform) to obtain 0.4 g of the desired product which was a pale yellow liquid.
[0035]
【The invention's effect】
The novel 6- (1-fluoroethyl) -5-iodo-4-pyrimidone of the present invention is useful as an intermediate for pharmaceuticals and agricultural chemicals.

Claims (2)

次式(1):
Figure 0004449211
(式中、*は不斉炭素原子を表す。)
で示される6−(1−フルオロエチル)−5−ヨード−4−ピリミドン。
The following formula (1):
Figure 0004449211
(In the formula, * represents an asymmetric carbon atom.)
6- (1-fluoroethyl) -5-iodo-4-pyrimidone represented by
次式(2):
Figure 0004449211
(式中、*は不斉炭素原子を表す。)
で示される6−(1−フルオロエチル)−4−ピリミドンと
次式(3):
Figure 0004449211
(式中、Xは塩素原子又は臭素原子を表す。)
で示されるハロゲン化ヨウ素とを反応させることを特徴とする請求項1記載の式(1)に記載の6−(1−フルオロエチル)−5−ヨード−4−ピリミドンの製法。
Formula (2):
Figure 0004449211
(In the formula, * represents an asymmetric carbon atom.)
6- (1-fluoroethyl) -4-pyrimidone represented by the following formula (3):
Figure 0004449211
(In the formula, X represents a chlorine atom or a bromine atom.)
A process for producing 6- (1-fluoroethyl) -5-iodo-4-pyrimidone according to formula (1) according to claim 1, characterized in that it is reacted with iodine halide represented by formula (1).
JP2000384776A 2000-12-19 2000-12-19 6- (1-fluoroethyl) -5-iodo-4-pyrimidone and process for producing the same Expired - Fee Related JP4449211B2 (en)

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