JPH04117367A - Fluoroalkyl group-containing pyrimidine derivative and production thereof - Google Patents
Fluoroalkyl group-containing pyrimidine derivative and production thereofInfo
- Publication number
- JPH04117367A JPH04117367A JP2234572A JP23457290A JPH04117367A JP H04117367 A JPH04117367 A JP H04117367A JP 2234572 A JP2234572 A JP 2234572A JP 23457290 A JP23457290 A JP 23457290A JP H04117367 A JPH04117367 A JP H04117367A
- Authority
- JP
- Japan
- Prior art keywords
- pyrimidine
- dimethoxy
- fluoroalkyl group
- formula
- 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.)
- Granted
Links
- 150000003230 pyrimidines Chemical class 0.000 title claims description 21
- 125000003709 fluoroalkyl group Chemical group 0.000 title claims description 20
- 238000004519 manufacturing process Methods 0.000 title claims description 17
- -1 diphenyl-tert- butylsilyl Chemical group 0.000 claims abstract description 29
- 150000002978 peroxides Chemical class 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 10
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 7
- 125000004665 trialkylsilyl group Chemical group 0.000 claims abstract description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000005252 haloacyl group Chemical group 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims 3
- 239000003905 agrochemical Substances 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000003443 antiviral agent Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 3
- HRGOWFDGTNQUSU-UHFFFAOYSA-N 2,4-dimethoxy-5-(trifluoromethyl)pyrimidine Chemical compound COC1=NC=C(C(F)(F)F)C(OC)=N1 HRGOWFDGTNQUSU-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003327 cancerostatic effect Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 150000003222 pyridines Chemical class 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- JUTIIYKOQPDNEV-UHFFFAOYSA-N 2,2,3,3,4,4,4-heptafluorobutanoyl 2,2,3,3,4,4,4-heptafluorobutaneperoxoate Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(=O)OOC(=O)C(F)(F)C(F)(F)C(F)(F)F JUTIIYKOQPDNEV-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- KEVRHVMWBKFGLO-UHFFFAOYSA-N 2,4-dimethoxypyrimidine Chemical compound COC1=CC=NC(OC)=N1 KEVRHVMWBKFGLO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- FSBNTQRWSOTNEW-UHFFFAOYSA-N Pyrimidine, 2,4- bis[(trimethylsilyl)oxy]- Chemical compound C[Si](C)(C)OC1=CC=NC(O[Si](C)(C)C)=N1 FSBNTQRWSOTNEW-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- AJDIZQLSFPQPEY-UHFFFAOYSA-N 1,1,2-Trichlorotrifluoroethane Chemical compound FC(F)(Cl)C(F)(Cl)Cl AJDIZQLSFPQPEY-UHFFFAOYSA-N 0.000 description 2
- UMSHFJBGHRSJRP-UHFFFAOYSA-N 5-(1,1,2,2,3,3,3-heptafluoropropyl)-2,4-dimethoxypyrimidine Chemical compound COC1=NC=C(C(F)(F)C(F)(F)C(F)(F)F)C(OC)=N1 UMSHFJBGHRSJRP-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007809 chemical reaction catalyst Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- ICGJEQXHHACFAH-UHFFFAOYSA-N (2,2,2-trifluoroacetyl) 2,2,2-trifluoroethaneperoxoate Chemical compound FC(F)(F)C(=O)OOC(=O)C(F)(F)F ICGJEQXHHACFAH-UHFFFAOYSA-N 0.000 description 1
- SLGOCMATMKJJCE-UHFFFAOYSA-N 1,1,1,2-tetrachloro-2,2-difluoroethane Chemical compound FC(F)(Cl)C(Cl)(Cl)Cl SLGOCMATMKJJCE-UHFFFAOYSA-N 0.000 description 1
- UGCSPKPEHQEOSR-UHFFFAOYSA-N 1,1,2,2-tetrachloro-1,2-difluoroethane Chemical compound FC(Cl)(Cl)C(F)(Cl)Cl UGCSPKPEHQEOSR-UHFFFAOYSA-N 0.000 description 1
- KTULQNFKNLFOHL-UHFFFAOYSA-N 1,2-dibromo-1,1,2,3,3,3-hexafluoropropane Chemical compound FC(F)(F)C(F)(Br)C(F)(F)Br KTULQNFKNLFOHL-UHFFFAOYSA-N 0.000 description 1
- OVZATIUQXBLIQT-UHFFFAOYSA-N 1,2-dibromo-1-chloro-1,2,2-trifluoroethane Chemical compound FC(F)(Br)C(F)(Cl)Br OVZATIUQXBLIQT-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- ZPGMWBFCBUKITA-UHFFFAOYSA-N 2,2,3-trichloro-1,1,1,3,4,4,4-heptafluorobutane Chemical compound FC(F)(F)C(F)(Cl)C(Cl)(Cl)C(F)(F)F ZPGMWBFCBUKITA-UHFFFAOYSA-N 0.000 description 1
- QBXWGANCZVGATM-UHFFFAOYSA-N 2,4-dibutoxypyrimidine Chemical compound CCCCOC1=CC=NC(OCCCC)=N1 QBXWGANCZVGATM-UHFFFAOYSA-N 0.000 description 1
- GEWCUVLRHIXPLH-UHFFFAOYSA-N 2,4-dimethoxy-5-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)pyrimidine Chemical compound COc1ncc(c(OC)n1)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F GEWCUVLRHIXPLH-UHFFFAOYSA-N 0.000 description 1
- LJODWHMHKHLDLM-UHFFFAOYSA-N 2,4-dipropoxypyrimidine Chemical compound CCCOC1=CC=NC(OCCC)=N1 LJODWHMHKHLDLM-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102100030500 Heparin cofactor 2 Human genes 0.000 description 1
- 101001082432 Homo sapiens Heparin cofactor 2 Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- KVBKAPANDHPRDG-UHFFFAOYSA-N dibromotetrafluoroethane Chemical compound FC(F)(Br)C(F)(F)Br KVBKAPANDHPRDG-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- KLABGSLRJVKZDX-UHFFFAOYSA-N triethyl-(2-triethylsilyloxypyrimidin-4-yl)oxysilane Chemical compound CC[Si](CC)(CC)OC1=CC=NC(O[Si](CC)(CC)CC)=N1 KLABGSLRJVKZDX-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、フルオロアルキル基含有ピリミジン誘導体及
びその製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a fluoroalkyl group-containing pyrimidine derivative and a method for producing the same.
〈従来の技術〉
有機化合物中に、フルオロアルキル基を含有する化合物
は、耐熱性、撥水撥油性、生理活性等の有用な性質を示
すものとして注目を集めている。<Prior Art> Among organic compounds, compounds containing a fluoroalkyl group are attracting attention as they exhibit useful properties such as heat resistance, water and oil repellency, and physiological activity.
特にピリミジン化合物中に、フルオロアルキル基が導入
されたフルオロアルキル基含有ピリミジン誘導体は、医
薬、農薬等として、特に制癌剤あるいは坑ウィルス剤の
合成中間体として有用であると考えられ注目されている
。しかしながら前記フルオロアルキル基含有ピリミジン
誘導体及びその製造方法については殆ど知られていない
のが現状である。In particular, pyrimidine derivatives containing a fluoroalkyl group, in which a fluoroalkyl group is introduced into a pyrimidine compound, are attracting attention because they are thought to be useful as medicines, agricultural chemicals, etc., and especially as synthetic intermediates for anticancer agents or antiviral agents. However, at present, little is known about the fluoroalkyl group-containing pyrimidine derivatives and their production methods.
〈発明が解決しようとする課題〉
本発明の目的は、医薬、農薬等の合成中間体として利用
可能なフルオロアルキル基含有ピリミジン誘導体及びそ
の製造方法を提供することにある。<Problems to be Solved by the Invention> An object of the present invention is to provide a fluoroalkyl group-containing pyrimidine derivative that can be used as a synthetic intermediate for medicines, agricultural chemicals, etc., and a method for producing the same.
本発明の別の目的は、反応触媒及び特殊な装置を用いず
、高収率かつ容易にフルオロアルキル基含有ピリミジン
誘導体を製造する方法を提供することにある。Another object of the present invention is to provide a method for easily producing a fluoroalkyl group-containing pyrimidine derivative in high yield without using a reaction catalyst or special equipment.
く課題を解決するための手段〉
本発明によれば、下記一般式（Ｉ）
（式中Ｒ１は、水素原子又は炭素数１〜４のアルキル基
を示し、Ｘはフッ素原子、塩素原子又は水素原子を示す
。但しＲｏが水素原子の場合、Ｘは水素原子又は塩素原
子である。ｎは１〜１０の整数を示す）で表わされるフ
ルオロアルキル基含有ピリミジン誘導体が提供される。According to the present invention, the following general formula (I) (wherein R1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and X represents a fluorine atom, a chlorine atom, or a hydrogen atom) (wherein, when Ro is a hydrogen atom, X is a hydrogen atom or a chlorine atom, and n is an integer of 1 to 10).
また本発明によれば、下記一般式（Ｉｔ）を示し、また
ｎは１〜１０の整数を示す）で表わされるジ（ハロアシ
ル）ペルオキシドと、下記一般式（ｍ）
（式中Ｒ２は、
炭素数１〜４のアルキル基、
トリ
アルキルシリル基又はジフェニル−し−ブチルシリル基
を示す）で表わされるピリミジン類とを反応させること
を特徴とする前記フルオロアルキル基含有ピリミジン誘
導体の製造方法が提供される。Further, according to the present invention, a di(haloacyl) peroxide represented by the following general formula (It), and n is an integer of 1 to 10), and a di(haloacyl) peroxide represented by the following general formula (m) (wherein R2 is carbon Provided is a method for producing the above-mentioned fluoroalkyl group-containing pyrimidine derivative, which comprises reacting the pyrimidine with a pyrimidine represented by a number 1 to 4 alkyl group, trialkylsilyl group, or diphenyl-butylsilyl group. .
以下本発明を更に詳細に説明する。The present invention will be explained in more detail below.
本発明のフルオロアルキル基含有ピリミジン誘導体は、
下記一般式（Ｉ）で表わすことができ、式中Ｒ１は、水
素原子又は炭素数１〜４のアルキル基を示し、Ｘは、フ
ッ素原子、塩素原子又は水素原子を示す。但しＲ□が水
素原子の場合、Ｘは水素原子又は塩素原子である。また
ｎは１〜１゜の整数を示す。この際Ｒ工が炭素数５以上
のアルキル基の場合には製造が困難であり、前記ｎが１
１以上の場合には、溶媒に対する溶解性が低下するので
使用できない。前記一般式（Ｉ）で表わされるフルオロ
アルキル基含有ピリミジン誘導体としては、例えば、２
，４−ジメトキシ−５−トリフルオロメチルピリミジン
、２．４−ジメトキシ−５−ペンタフルオロエチルピリ
ミジン、２，４−ジメトキシ−５−ヘプタフルオロプロ
ピルピリミジン、２，４−ジメトキシ−５−ノナフルオ
ロブチルピリミジン、２，４−ジメトキシ−５−ウンデ
カフルオロペンチルピリミジン、２，４−ジメトキシ−
５−トリデカフルオロへキシルピリミジン、２，４−ジ
メトキシ−５−ペンタデカフルオロヘプチルピリミジン
、２，４−ジメトキシ−５−クロロジフルオロメチルピ
リミジン、２，４−ジメトキシ−５−（２’ −クロロ
テトラフルオロエチル）ピリミジン、２，４−ジメトキ
シ−５−（３′−クロロへキサフルオロプロピル）ピリ
ミジン、２，４−ジメトキシ−５−（４’ −クロロオ
クタフルオロブチル）ピリミジン、２．４−ジメトキシ
−５−（５’ −クロロデカフルオロペンチル）ピリミ
ジン、２，４−ジメトキシ−５−（６′−クロロドデカ
フルオロヘキシル）ピリミジン、２，４−ジメトキシ−
５−（７’ −クロロテトラデカフルオロヘプチル）ピ
リミジン、２゜４−ジメトキシ−５−ヒドロジフルオロ
メチルピリミジン、２，４−ジメトキシ−５−（２″−
ヒドロテトラフルオロエチル）ピリミジン、２，４−ジ
メトキシ−５−（３’ −ヒドロへキサフルオロプロピ
ル）ピリミジン、２，４−ジメトキシ−５−（４’−ヒ
ドロオクタフルオロブチル）ピリミジン、２，４−ジメ
トキシ−５−（５’ −ヒドロデカフルオロペンチル）
ピリミジン、２，４−ジメトキシ−５−（６″−ヒドロ
ドデカフルオロヘキシル）ピリミジン、２，４−ジメト
キシ−５−（７′−ヒドロテトラデカフルオロヘプチル
）ピリミジン、２，４−ジヒドロキシ−５−クロロジフ
ルオロメチルピリミジン、２，４−ジヒドロキシ−５−
（２’ −クロロテトラフルオロエチル）ピリミジン、
２，４−ジヒドロキシ−５−（３’−クロロへキサフル
オロプロピル）ピリミジン、２．４−ジヒドロキシ−５
−（４’−クロロオクタフルオロブチル）ピリミジン、
２，４−ジヒドロキシ−５−（５’ −クロロデカフル
オロペンチル）ピリミジン、２，４−ジヒドロキシ−５
−（６′−クロロドデカフルオロヘキシル）ピリミジン
、２，４−ジヒドロキシ−５−（７’ −クロロテトラ
デカフルオロヘプチル）ピリミジン、２゜４−ジヒドロ
キシ−５−ヒドロジフルオロメチルピリミジン、２，４
−ジヒドロキシ−５−（２’−ヒドロテトラフルオロエ
チル）ピリミジン、２゜４−ジヒドロキシ−５−（３’
−ヒドロへキサフルオロプロピル）ピリミジン、２，
４−ジヒドロキシ−５−（４’ −ヒドロオクタフルオ
ロブチル）ピリミジン、２，４−ジヒドロキシ−５−（
５’−ヒドロデカフルオロペンチル）ピリミジン、２゜
４−ジヒドロキシ−５−（６’ −ヒドロドデカフルオ
ロヘキシル）ピリミジン、２，４−ジヒドロキシ−５−
（７’ −ヒドロテトラデカフルオロヘプチル）ピリミ
ジン等を好ましく挙げることができる。The fluoroalkyl group-containing pyrimidine derivative of the present invention is
It can be represented by the following general formula (I), where R1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and X represents a fluorine atom, a chlorine atom, or a hydrogen atom. However, when R□ is a hydrogen atom, X is a hydrogen atom or a chlorine atom. Further, n represents an integer of 1 to 1°. In this case, if R is an alkyl group having 5 or more carbon atoms, production is difficult, and n is 1.
If it is 1 or more, it cannot be used because the solubility in the solvent decreases. Examples of the fluoroalkyl group-containing pyrimidine derivative represented by the general formula (I) include 2
, 4-dimethoxy-5-trifluoromethylpyrimidine, 2,4-dimethoxy-5-pentafluoroethylpyrimidine, 2,4-dimethoxy-5-heptafluoropropylpyrimidine, 2,4-dimethoxy-5-nonafluorobutylpyrimidine , 2,4-dimethoxy-5-undecafluoropentylpyrimidine, 2,4-dimethoxy-
5-tridecafluorohexylpyrimidine, 2,4-dimethoxy-5-pentadecafluoroheptylpyrimidine, 2,4-dimethoxy-5-chlorodifluoromethylpyrimidine, 2,4-dimethoxy-5-(2'-chlorotetra fluoroethyl)pyrimidine, 2,4-dimethoxy-5-(3'-chlorohexafluoropropyl)pyrimidine, 2,4-dimethoxy-5-(4'-chlorooctafluorobutyl)pyrimidine, 2,4-dimethoxy- 5-(5'-chlorodecafluoropentyl)pyrimidine, 2,4-dimethoxy-5-(6'-chlorododecafluorohexyl)pyrimidine, 2,4-dimethoxy-
5-(7'-chlorotetradecafluoroheptyl)pyrimidine, 2゜4-dimethoxy-5-hydrodifluoromethylpyrimidine, 2,4-dimethoxy-5-(2''-
hydrotetrafluoroethyl)pyrimidine, 2,4-dimethoxy-5-(3'-hydrohexafluoropropyl)pyrimidine, 2,4-dimethoxy-5-(4'-hydrooctafluorobutyl)pyrimidine, 2,4- Dimethoxy-5-(5'-hydrodecafluoropentyl)
Pyrimidine, 2,4-dimethoxy-5-(6″-hydrododecafluorohexyl)pyrimidine, 2,4-dimethoxy-5-(7′-hydrotetradecafluoroheptyl)pyrimidine, 2,4-dihydroxy-5-chloro Difluoromethylpyrimidine, 2,4-dihydroxy-5-
(2'-chlorotetrafluoroethyl)pyrimidine,
2,4-dihydroxy-5-(3'-chlorohexafluoropropyl)pyrimidine, 2,4-dihydroxy-5
-(4'-chlorooctafluorobutyl)pyrimidine,
2,4-dihydroxy-5-(5'-chlorodecafluoropentyl)pyrimidine, 2,4-dihydroxy-5
-(6'-chlorododecafluorohexyl)pyrimidine, 2,4-dihydroxy-5-(7'-chlorotetradecafluoroheptyl)pyrimidine, 2°4-dihydroxy-5-hydrodifluoromethylpyrimidine, 2,4
-dihydroxy-5-(2'-hydrotetrafluoroethyl)pyrimidine, 2°4-dihydroxy-5-(3'
-hydrohexafluoropropyl)pyrimidine, 2,
4-dihydroxy-5-(4'-hydrooctafluorobutyl)pyrimidine, 2,4-dihydroxy-5-(
5'-hydrodecafluoropentyl)pyrimidine, 2゜4-dihydroxy-5-(6'-hydrododecafluorohexyl)pyrimidine, 2,4-dihydroxy-5-
Preferred examples include (7'-hydrotetradecafluoroheptyl)pyrimidine.
本発明におけるフルオロアルキル基含有ピリミジン誘導
体の製造方法は、特定のジ（ハロアシル）ペルオキシド
と特定のピリミジン類とを反応させることを特徴とする
。The method for producing a fluoroalkyl group-containing pyrimidine derivative in the present invention is characterized by reacting a specific di(haloacyl)peroxide with a specific pyrimidine.
本発明の製造方法において原料成分として用いるジ（ハ
ロアシル）ペルオキシドは下記一般式％式％
式中Ｘは、フッ素原子、塩素原子又は水素原子を示し、
またｎは１〜１０の整数を示す。この際ｎが１１以上の
場合には、溶媒の存在下において反応させる際に前記ジ
（ハロアシル）ペルオキシドの溶解性に問題が生じるの
で使用できない。前記一般式（ＩＩ）で表わされるジ（
ハロアシル）ペルオキシドのＸ（ＣＦ、＋□を、具体的
に列挙すると、ＣＦ ３−２Ｆ （ＣＦ ２ ＋ ｚ
−Ｆ （ＣＦ ２ ＋ ａ 。The di(haloacyl)peroxide used as a raw material component in the production method of the present invention has the following general formula %, where X represents a fluorine atom, a chlorine atom, or a hydrogen atom,
Moreover, n represents an integer of 1 to 10. In this case, if n is 11 or more, the di(haloacyl)peroxide cannot be used because a problem arises in the solubility of the di(haloacyl)peroxide when the reaction is carried out in the presence of a solvent. Di(
Specifically enumerating X(CF, +□ of haloacyl) peroxide, CF 3-2F (CF 2 + z
−F (CF 2 + a.
Ｆ（ＣＦ２＋。、Ｆ （ｃ Ｆ２＋ｓ。F(CF2+., F(cF2+s.
Ｆ（ＣＦ２＋、、 Ｆ（ｃｐ、＋ｔ。F(CF2+,, F(cp, +t.
Ｆ（ＣＦ２＋、、Ｆ（ＣＦ、＋９゜ Ｆ （ＣＦ２＋、、、 ＣＩ ＣＦ２ Ｃｌ （ＣＦ２＋、、 Ｃｌ （ＣＦ、＋、。F(CF2+,,F(CF,+9° F (CF2+, CI CF2 Cl (CF2+,, Cl (CF,+,.
Ｃｌ （ＣＦＺ ＋＊、Ｃｌ （ＣＦ２ ＋ ｓ。Cl (CFZ +*, Cl (CF2 + s.
Ｃｌ （ＣＦ２＋、、 Ｃｌ （ＣＦ２−）−、。Cl (CF2+,, Cl (CF2-)-,.
Ｃｌ （ＣＦ２＋、、 Ｃｌ （ＣＦ２＋９゜Ｃｌ （
ＣＦ、＋、。、ＨＣＦ２
Ｈ（ＣＦｚ ＋ ２．Ｈ（ＣＦ２ ＋ ３゜Ｈ（ＣＦ２
＋４．Ｈ（ＣＦ、＋、。Cl (CF2+,, Cl (CF2+9゜Cl (
CF,+,. , HCF2 H(CFz + 2.H(CF2 + 3°H(CF2
+4. H(CF, +,.
Ｈ（ＣＦ２＋１８ Ｈ（ＣＦ２＋７゜ Ｈ（ＣＦ ２ ＋ ｓｒ 、Ｈ（ＣＦ ２ ＋ ｓ 。H(CF2+18 H(CF2+7゜ H(CF 2 + sr, H(CF 2 + s.
Ｈ（ＣＦ２＋１８である。H(CF2+18.
本発明の製造方法において、前記ジ（ハロアシル）ペル
オキシドと反応させるピリミジン類は、下記一般式（Ｉ
ｎ）で表わすことができ、式中Ｒ２は、炭素数１〜４の
アルキル基、トリアルキルシリル基又はジフェニル−ｔ
−ブチルシリル基を示す。この際、Ｒ２が、炭素数５以
上のアルキル基若しくは炭素数５以上のアルキル基を有
するトリアルキルシリル基の場合には製造が困難である
。In the production method of the present invention, the pyrimidine to be reacted with the di(haloacyl)peroxide has the following general formula (I
n), where R2 is an alkyl group having 1 to 4 carbon atoms, a trialkylsilyl group, or a diphenyl-t
-Represents a butylsilyl group. At this time, production is difficult if R2 is an alkyl group having 5 or more carbon atoms or a trialkylsilyl group having an alkyl group having 5 or more carbon atoms.
前記一般式（ＩＩ［）で表わされるピリミジン化合物と
しては、例えば２，４−ジメトキシピリミジン、２，４
−ジェトキシピリミジン、２，４−ジプロポキシピリミ
ジン、２，４−ジブトキシピリミジン、２，４−ビス（
ジフェニル−ｔ−ブチルシロキシ）ピリミジン、２，４
−ビス（トリメチルシロキシ）ピリミジン、２，４−ビ
ス（トリエチルシロキシ）ピリミジン、２，４−ビス（
トリプロピルシロキシ）ピリミジン、２，４−ビス（ト
リブチルシロキシ）ピリミジン等を好ましく挙げること
ができる。Examples of the pyrimidine compound represented by the general formula (II[) include 2,4-dimethoxypyrimidine, 2,4-dimethoxypyrimidine, and 2,4-dimethoxypyrimidine.
-jethoxypyrimidine, 2,4-dipropoxypyrimidine, 2,4-dibutoxypyrimidine, 2,4-bis(
diphenyl-t-butylsiloxy)pyrimidine, 2,4
-bis(trimethylsiloxy)pyrimidine, 2,4-bis(triethylsiloxy)pyrimidine, 2,4-bis(
Preferred examples include tripropylsiloxy)pyrimidine and 2,4-bis(tributylsiloxy)pyrimidine.
本発明の製造方法において、前記ジ（ハロアシル）ペル
オキシドと前記ピリミジン類との仕込みモル比は、１：
０．２〜１０が好ましく、特に１：０．５〜５であるこ
とが好ましい。前記ピリミジン類の仕込みモル比が０．
２未満の場合には、生成するフルオロアルキル基含有ピ
リミジン誘導体の収率が低下し、また１０を超える場合
には反応終了後において未反応のピリミジン類が多量に
残存し、目的とする生成物の単離が困難となるので好ま
しくない。また、反応は常圧で行なうことが可能であり
、且つ反応温度は一２０〜＋１５０℃の範囲が好ましく
、０〜１００°Ｃの範囲が特に好ましい。前記反応温度
が一２０°Ｃ未満の場合には反応時間に長時間を要し、
１５０℃を超えると反応時の圧力が高くなり、反応操作
が困難であるので好ましくない。更に反応時間は３０分
〜２０時間の範囲が好ましく、工業的には３〜１０時間
の範囲とするのが特に好ましい。In the production method of the present invention, the molar ratio of the di(haloacyl)peroxide and the pyrimidine is 1:
The ratio is preferably 0.2 to 10, particularly preferably 1:0.5 to 5. The molar ratio of the pyrimidines charged is 0.
If it is less than 2, the yield of the fluoroalkyl group-containing pyrimidine derivative to be produced will decrease, and if it is more than 10, a large amount of unreacted pyrimidines will remain after the reaction is completed, and the desired product will not be produced. This is not preferred because isolation becomes difficult. Further, the reaction can be carried out at normal pressure, and the reaction temperature is preferably in the range of -20 to +150°C, particularly preferably in the range of 0 to 100°C. When the reaction temperature is less than 120°C, the reaction time takes a long time,
If the temperature exceeds 150°C, the pressure during the reaction will be high and the reaction operation will be difficult, which is not preferable. Further, the reaction time is preferably in the range of 30 minutes to 20 hours, and industrially particularly preferably in the range of 3 to 10 hours.
本発明の製造方法では、前記種々の反応条件下において
、前記ジ（ハロアシル）ペルオキシドと前記ピリミジン
類とを反応させることにより、目的とするフルオロアル
キル基含有ピリミジン誘導体を製造することができるが
、前記ジ（ハロアシル）ペルオキシドの取扱い及び反応
をより円滑に行なうために、溶媒を用いて反応させるの
が好ましい。前記溶媒としてはハロゲン化脂肪族溶媒、
具体的には例えば、２−クロロ−１，２−ジブロモ−１
，１，２−トリフルオロエタン、１，２−ジブロモへキ
サフルオロプロパン、１，２−ジブロモテトラフルオロ
エタン、１，１−ジフルオロテトラクロロエタン、１，
２−ジフルオロテトラクロロエタン、フルオロトリクロ
ロメタン、ヘプタフルオロ−２，３，３−トリクロロブ
タン、１゜１．１．３−テトラクロロテトラフルオロプ
ロパン、１，１．１−）−ツクロロペンタフルオロプロ
パン、１，１．２−トリクロロトリフルオロエタン等を
好ましく挙げることができ、特に工業的には、１，１．
２−トリクロロトリフルオロエタンが好ましい。また前
記溶媒の仕込み量は、前記フルオロアルカノイルの濃度
が前記溶媒に対して１〜３０重量％の範囲となるように
調整するのが望ましい。In the production method of the present invention, the desired fluoroalkyl group-containing pyrimidine derivative can be produced by reacting the di(haloacyl)peroxide with the pyrimidine under the various reaction conditions. In order to handle and react the di(haloacyl)peroxide more smoothly, it is preferable to carry out the reaction using a solvent. The solvent includes a halogenated aliphatic solvent,
Specifically, for example, 2-chloro-1,2-dibromo-1
, 1,2-trifluoroethane, 1,2-dibromohexafluoropropane, 1,2-dibromotetrafluoroethane, 1,1-difluorotetrachloroethane, 1,
2-difluorotetrachloroethane, fluorotrichloromethane, heptafluoro-2,3,3-trichlorobutane, 1゜1.1.3-tetrachlorotetrafluoropropane, 1,1.1-)-dichloropentafluoropropane, Preferred examples include 1,1.2-trichlorotrifluoroethane, and particularly from an industrial perspective, 1,1.
2-Trichlorotrifluoroethane is preferred. Further, the amount of the solvent charged is desirably adjusted so that the concentration of the fluoroalkanoyl is in the range of 1 to 30% by weight based on the solvent.
また、前記一般式（Ｉ）で表わされるフルオロアルキル
基含有ピリミジン誘導体において、Ｒ。Further, in the fluoroalkyl group-containing pyrimidine derivative represented by the general formula (I), R.
が水素原子のものは、前記製造方法の他に、前記製造方
法により得られたＲ１がアルキル基であるフルオロアル
キル基含有ピリミジン誘導体をヨウ化ナトリウムの存在
下、氷酢酸などの酸性条件下にて処理することによって
も得ることができる。is a hydrogen atom, in addition to the above production method, a fluoroalkyl group-containing pyrimidine derivative in which R1 is an alkyl group obtained by the above production method is subjected to acidic conditions such as glacial acetic acid in the presence of sodium iodide. It can also be obtained by processing.
本発明の製造法によりえられる反応生成物は蒸留、カラ
ムクロマトグラフィー、再結晶法等の公知の方法で精製
することが可能である。The reaction product obtained by the production method of the present invention can be purified by known methods such as distillation, column chromatography, and recrystallization.
〈発明の効果〉
本発明のフルオロアルキル基含有ピリミジン誘導体は、
医薬、農薬等として、特に制癌剤及び坑ウィルス剤の合
成中間体として有用である。また本発明の製造方法にお
いては、短時間で高収率かつ容易に、しかも反応触媒及
び特殊な装置を使用せずにフルオロアルキル基含有ピリ
ミジン誘導体を製造することができる。<Effects of the invention> The fluoroalkyl group-containing pyrimidine derivative of the present invention is
It is useful as a medicine, agrochemical, etc., especially as a synthetic intermediate for anticancer agents and antiviral agents. Further, in the production method of the present invention, a fluoroalkyl group-containing pyrimidine derivative can be produced easily in a short time with high yield and without using a reaction catalyst or special equipment.
〈実施例〉
以下本発明を実施例により更に詳しく説明するが、本発
明はこれらに限定されるものではない。<Examples> The present invention will be explained in more detail below with reference to Examples, but the present invention is not limited thereto.
失隨旌よ
アルゴン雰囲気下にて、２，４−ビス（トリメチルシロ
キシ）ピリミジン１．２８ｇを１，１゜２−トリクロロ
トリフルオロエタン２０ｍＱに溶解した。次いで得られ
た溶液の温度を３０℃に保ち、ビス（ヘプタフルオロブ
チリル）ベルオキシド１．１ｇ（ピリミジン類に対して
０．５倍当量）を含む１，１．２−トリクロロトリフル
オロエタン溶液２１．６ｇを滴下漏斗より約１分間かけ
て滴下した。次いで同温度にて、３時間撹拌を行なった
後、２時間還流を行なった。反応終了後、反応混合物を
室温まで冷却し、水１００ｍＱを加えて、２時間撹拌し
た。次いで酢酸エチル１５０ｍＱを加えて抽出を行ない
、有機層を飽和炭酸水素ナトリウム水溶液で洗浄した後
、硫酸ナトリウムを用いて乾燥した。最終に、カラムク
ロマトグラフィーにより精製を行ない、２，４−ジヒド
ロキシ−５−へブタフルオロプロピルピリミジンを０．
４０ｇ（収率５７％）得た。得られた化合物の各種分析
結果について以下に示す。Sorry, under an argon atmosphere, 1.28 g of 2,4-bis(trimethylsiloxy)pyrimidine was dissolved in 20 mQ of 1,1°2-trichlorotrifluoroethane. Next, the temperature of the obtained solution was maintained at 30°C, and a 1,1,2-trichlorotrifluoroethane solution containing 1.1 g of bis(heptafluorobutyryl) peroxide (0.5 times equivalent to pyrimidines) was added. 21.6 g was added dropwise from the dropping funnel over about 1 minute. Next, the mixture was stirred at the same temperature for 3 hours, and then refluxed for 2 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, 100 mQ of water was added, and the mixture was stirred for 2 hours. Next, 150 mQ of ethyl acetate was added to perform extraction, and the organic layer was washed with a saturated aqueous sodium bicarbonate solution and then dried using sodium sulfate. Finally, purification was performed by column chromatography to obtain 2,4-dihydroxy-5-hebutafluoropropylpyrimidine at 0.0%.
40 g (yield 57%) was obtained. Various analysis results of the obtained compound are shown below.
ｍｐ：２５８〜２５９℃
ＭＳ ｖｒ／ｚ ２８０（Ｍ”）、２６１，１６１１Ｒ
（ｃｍ−” ）３１６０ （ＮＨ） 、１６８０．１７
５０ （Ｃ＝０） 、１３６０ （ＣＦ３） 。mp: 258-259°C MS vr/z 280 (M”), 261,1611R
(cm-”)3160 (NH), 1680.17
50 (C=0), 1360 (CF3).
１２３０（ＣＦ２）
１Ｈ−ＮＭＲ（ｄ’−ＤＭＳＯ）δ ７，９９（ｓ、Ｌ
Ｈ）” Ｆ−ＮＭＲ（ｄ’ −ＤＭＳＯ；ｅｘｔ 、
ＣＦ３ＣＯ０Ｈ）δ −１，５２（３Ｆ、ｔ、Ｊ＝８．
６８．γ−ＣＦ、）、−３０，６７（２Ｆ、、ｑ。1230 (CF2) 1H-NMR (d'-DMSO) δ 7,99 (s, L
H)"F-NMR (d'-DMSO;ext,
CF3CO0H) δ −1,52 (3F, t, J=8.
68. γ-CF, ), -30,67 (2F,,q.
Ｊ＝９．９３．ａ−ＣＦ２）、−４６，８７（２Ｆ、ｓ
、β−ＣＦ２）なお、得られた２、４−ジヒドロキシ−
５−へブタフルオロプロピルピリミジンは、以下に示す
ように、５−へブタフルオロウラシルの互変異性体であ
る。J=9.93. a-CF2), -46,87 (2F, s
, β-CF2) In addition, the obtained 2,4-dihydroxy-
5-Hebutafluoropropylpyrimidine is a tautomer of 5-hebutafluorouracil, as shown below.
ビス（ヘプタフルオロブチリル）ペルオキシドをビス（
ペンタデカフルオロヘプタノイル）ペルオキシドに代え
た以外は、実施例１と同様にして反応及び精製を行ない
、２，４−ジヒドロキシ−５−ペンタデカフルオロヘキ
シルピリミジンを０゜６７ｇ（収率３８％）得た。 分
析結果を以下に示す。Bis(heptafluorobutyryl) peroxide is converted to bis(heptafluorobutyryl) peroxide.
The reaction and purification were carried out in the same manner as in Example 1, except that pentadecafluoroheptanoyl) peroxide was used, and 0.67 g (yield: 38%) of 2,4-dihydroxy-5-pentadecafluorohexylpyrimidine was obtained. Ta. The analysis results are shown below.
ｍｐ：２７７−２７８℃
ＭＳ ｖａ／ｚ ４３０（Ｍ”）、４１１，１６１１Ｒ
（ｃｍ−１）３２４０（Ｎｉｌ） 、１６７０，１７６
０（Ｃ＝ｏ） 、１３２５（ＣＦ３）１２５５（ＣＦ２
）
” Ｈ−ＮＭＲ（ｄ’ −ＤＭＳＯ） δ ７．９８
（ｓ、ＬＨ）”Ｆ−ＮＭＲ（ｄ’−ＤＭＳＯ；ｅｘｔ、
ＣＦ３ＣＯ０Ｈ）δ −２，０８（３Ｆ、ｔ、Ｊ＝８．
６９．ζ−ＣＦ３） 、 −２９，９４（２Ｆ 、 ｔ
。mp: 277-278℃ MS va/z 430 (M”), 411,1611R
(cm-1) 3240 (Nil), 1670,176
0 (C=o), 1325 (CF3) 1255 (CF2
) ” H-NMR (d'-DMSO) δ 7.98
(s, LH)"F-NMR (d'-DMSO; ext.
CF3CO0H) δ -2,08 (3F, t, J=8.
69. ζ-CF3), -29,94(2F, t
.
Ｊ＝１３．６５． Ｅ −ＣＦ２）、−４２，６０（２
Ｆ、ｂｒ ｓ、δ−ＣＦ２）。J=13.65. E -CF2), -42,60(2
F, br s, δ-CF2).
−４３，３９（２Ｆ、ｂｒ ｓ、 ｙ−ＣＦ、）、−４
４，２１（２Ｆ、ｂｒ ｓ。-43,39 (2F, br s, y-CF,), -4
4,21 (2F, br s.
β−ＣＦ、）、−４７，５３（２Ｆ、ｑ、Ｊ＝７．４４
．α−ＣＦ２）去ＪＬｆＬ表
ビス（ヘプタフルオロブチリル）ペルオキシドの代わり
にビス（トリフルオロアセチル）ペルオキシドを用い、
反応温度を７０℃として反応を耐圧アンプル中で行なっ
た以外は実施例１と同様にして反応及び精製を行ない、
２．４−ジヒドロキシ−５−トリフルオロメチルピリミ
ジンを０．１７ｇ（収率３１％）得た。 分析結果を以
下に示す。β-CF, ), -47,53 (2F, q, J = 7.44
．． α-CF2) Using bis(trifluoroacetyl) peroxide instead of bis(heptafluorobutyryl) peroxide,
Reaction and purification were carried out in the same manner as in Example 1 except that the reaction temperature was 70°C and the reaction was carried out in a pressure-resistant ampoule.
0.17 g (yield 31%) of 2.4-dihydroxy-5-trifluoromethylpyrimidine was obtained. The analysis results are shown below.
ｍｐ：２３６−２３７℃
ＭＳ ｖｓ／ｚ １８０（Ｍ”）、１３７ＩＲ（ｃｍ−
”）３２４０（ＮＨ）、１６８０，１７１５，１７５０
（Ｃ＝Ｏ）。mp: 236-237℃ MS vs/z 180 (M”), 137IR (cm-
”) 3240 (NH), 1680, 1715, 1750
(C=O).
１３５０（ＣＦ２）
１Ｈ−ＮＭＲ（ｄ’−ＤＭＳＯ） δ ７．９８（ｓ
、１８）１ｓＦ−ＮＭＲ（ｄ’−ＤＭＳＯ；ｅｘｔ、Ｃ
Ｆ３Ｃｏｏ）Ｉ）６１６．９０（３Ｆ、ｓ）
夫１１引髪
ビス（ヘプタフルオロブチリル）ペルオキシドをビス（
クロロジフルオロアセチル）ペルオキシドに代えた以外
は実施例１と同様にして反応及び精製を行ない、２，４
−ジヒドロキシ−５−クロロジフルオロメチルピリミジ
ンを収率５０％で得た。 分析結果を以下に示す。1350 (CF2) 1H-NMR (d'-DMSO) δ 7.98 (s
, 18) 1sF-NMR (d'-DMSO; ext, C
F3Coo) I) 616.90 (3F, s) Husband 11 Bis(heptafluorobutyryl) peroxide is converted into bis(
The reaction and purification were carried out in the same manner as in Example 1 except that chlorodifluoroacetyl) peroxide was used, and 2,4
-dihydroxy-5-chlorodifluoromethylpyrimidine was obtained in a yield of 50%. The analysis results are shown below.
ＭＳ ｒｘ／ｚ １５７（Ｍ”）
ＩＲ（ａｍ’″１）３２４０（ＮＨ）、１６８０，１７
１５．１７５０（Ｃ＝Ｏ）。MS rx/z 157 (M") IR (am'"1) 3240 (NH), 1680, 17
15.1750 (C=O).
１２４０（ＣＦ、）
１）１−ＮＭＲ（ｄ’−ＤＭＳＯ）δ ７．９３（ｓ、
ＩＨ）１９Ｆ−ＮＭＲ（ｄ’−ＤＭＳＯ；ｅｘｔ、ＣＦ
、Ｃ００Ｈ）δ −３７，００（２Ｆ、ｓ）
来ｆｆ１
２，４−ビス（トリメチルシロキシ）ピリミジンを２，
４−ジメトキシピリミジンに代えた以外は、実施例１と
同様にして反応及び精製を行ない、２．４−ジメトキシ
−５−へブタフルオロプロピルピリミジンを０．７３ｇ
（収率４７％）得た。1240 (CF,) 1) 1-NMR (d'-DMSO) δ 7.93 (s,
IH) 19F-NMR (d'-DMSO; ext, CF
, C00H) δ -37,00 (2F, s) from ff1 2,4-bis(trimethylsiloxy)pyrimidine to 2,
The reaction and purification were carried out in the same manner as in Example 1 except that 4-dimethoxypyrimidine was used, and 0.73 g of 2.4-dimethoxy-5-hebutafluoropropylpyrimidine was obtained.
(yield 47%).
分析結果を以下に示す。The analysis results are shown below.
ｍｐ：２１４〜２１５℃
ＭＳ ｍ／ｚ ３０８（Ｍ”）、２７８，１８９ＩＲ（
ｃｍ−’″）１３４０（ＣＦ３）、１２３５（ＣＦ、）
１）１−ＮＭＲ（ｄ’−ＤＭＳＯ）δ４．０５（３Ｈ，
ｓ） 、４．０８（３Ｈ，ｓ） 。mp: 214-215℃ MS m/z 308 (M”), 278,189IR (
cm-''') 1340 (CF3), 1235 (CF, )
1) 1-NMR (d'-DMSO) δ4.05 (3H,
s), 4.08 (3H, s).
７．９９（Ｉ）１．ｓ）
１ｇＦ−ＮＭＲ（ｄ’ −ＤＭＳＯ；ｅｘｔ 、 ＣＦ
３ＣＯ０Ｈ）δ −３，３１（３Ｆ、ｔ、Ｊ＝９．９３
．γ−ＣＦ３）、−３２，６４（２Ｆ、ｑ。7.99(I)1. s) 1gF-NMR (d'-DMSO; ext, CF
3CO0H) δ −3,31 (3F, t, J=9.93
．． γ-CF3), -32,64 (2F, q.
Ｊ＝９．９２．α−ＣＦ２）、−４８，９３（２Ｆ、ｓ
、β−ＣＦ２）去】１１も
実施例５で得られた２、４−ジメトキシ−５ヘプタフル
オロプロピルピリミジン０．５０ｇを氷酢酸２０ｍＱに
添加し、更にヨウ化ナトリウム１．３４ｇ （２，４−
ジメトキシ−５−へブタフルオロプロピルピリミジンに
対して５倍モル量）を加えて、１００℃にて５時間反応
を行なった。J=9.92. α-CF2), -48,93(2F,s
, β-CF2) [11] 0.50 g of 2,4-dimethoxy-5heptafluoropropylpyrimidine obtained in Example 5 was added to 20 mQ of glacial acetic acid, and further 1.34 g of sodium iodide (2,4-
5 times the molar amount of dimethoxy-5-hebutafluoropropylpyrimidine) was added thereto, and the reaction was carried out at 100°C for 5 hours.
反応終了後、酢酸を除去し、得られた生成物をベンゼン
で洗浄した後、温水中に溶解した。次いでチオ硫酸ナト
リウムを加えた後水溶液を冷却して、２．４−ジヒドロ
キシ−５−へブタフルオロプロピルピリミジンを収率８
８％で得た。After the reaction was completed, acetic acid was removed, the resulting product was washed with benzene, and then dissolved in warm water. Next, sodium thiosulfate was added and the aqueous solution was cooled to obtain 2,4-dihydroxy-5-hebutafluoropropylpyrimidine in a yield of 8.
Obtained at 8%.
Claims (1)
基を示し、Ｘはフッ素原子、塩素原子又は水素原子を示
す。但しＲ＿１が水素原子の場合、Ｘは水素原子又は塩
素原子である。またｎは１〜１０の整数を示す）で表わ
されるフルオロアルキル基含有ピリミジン誘導体。 ２）下記一般式（II） ▲数式、化学式、表等があります▼・・・・（II） （式中Ｘは、フッ素原子、塩素原子又は水素原子を示し
、またｎは１〜１０の整数を示す）で表わされるジ（ハ
ロアシル）ペルオキシドと、下記一般式（III） ▲数式、化学式、表等があります▼・・・（III） （式中Ｒ＿２は、炭素数１〜４のアルキル基、トリアル
キルシリル基又はジフェニル−ｔ−ブチルシリル基を示
す）で表わされるピリミジン類とを反応させることを特
徴とする請求項１記載のフルオロアルキル基含有ピリミ
ジン誘導体の製造方法。[Claims] 1) The following general formula (I) ▲There are numerical formulas, chemical formulas, tables, etc.▼... (I) (In the formula, R_1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, X represents a fluorine atom, a chlorine atom, or a hydrogen atom.However, when R_1 is a hydrogen atom, X is a hydrogen atom or a chlorine atom.Fluoroalkyl group-containing pyrimidine represented by derivative. 2) General formula (II) below ▲Mathematical formulas, chemical formulas, tables, etc.▼・・・(II) (In the formula, X represents a fluorine atom, a chlorine atom, or a hydrogen atom, and n is an integer from 1 to 10. di(haloacyl) peroxide represented by the following general formula (III) ▲ Numerical formulas, chemical formulas, tables, etc. are available▼...(III) (In the formula, R_2 is an alkyl group having 1 to 4 carbon atoms, 2. The method for producing a fluoroalkyl group-containing pyrimidine derivative according to claim 1, wherein the pyrimidine derivative is reacted with a pyrimidine represented by a trialkylsilyl group or a diphenyl-t-butylsilyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2234572A JP3032781B2 (en) | 1990-09-06 | 1990-09-06 | Method for producing pyrimidine derivative containing fluoroalkyl group |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2234572A JP3032781B2 (en) | 1990-09-06 | 1990-09-06 | Method for producing pyrimidine derivative containing fluoroalkyl group |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04117367A true JPH04117367A (en) | 1992-04-17 |
| JP3032781B2 JP3032781B2 (en) | 2000-04-17 |
Family
ID=16973120
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2234572A Expired - Lifetime JP3032781B2 (en) | 1990-09-06 | 1990-09-06 | Method for producing pyrimidine derivative containing fluoroalkyl group |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3032781B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014510743A (en) * | 2011-03-31 | 2014-05-01 | シェファー、コンスタンツェ | Perfluorinated compounds for non-viral introduction of nucleic acids |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11572343B2 (en) | 2018-02-16 | 2023-02-07 | Daikin Industries, Ltd. | Perfluoro diacyl peroxide as polymerization initiator and polymer preparation method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3324126A (en) | 1963-08-07 | 1967-06-06 | Univ Kansas State | Production of 5-trifluoromethyluracil |
-
1990
- 1990-09-06 JP JP2234572A patent/JP3032781B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014510743A (en) * | 2011-03-31 | 2014-05-01 | シェファー、コンスタンツェ | Perfluorinated compounds for non-viral introduction of nucleic acids |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3032781B2 (en) | 2000-04-17 |
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