JPH11322749A - Production of opened cyclopropane ring compound - Google Patents
Production of opened cyclopropane ring compoundInfo
- Publication number
- JPH11322749A JPH11322749A JP10133349A JP13334998A JPH11322749A JP H11322749 A JPH11322749 A JP H11322749A JP 10133349 A JP10133349 A JP 10133349A JP 13334998 A JP13334998 A JP 13334998A JP H11322749 A JPH11322749 A JP H11322749A
- Authority
- JP
- Japan
- Prior art keywords
- group
- cyclopropane ring
- formate
- formula
- compound
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- -1 cyclopropane ring compound Chemical class 0.000 title abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 27
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 15
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 235000019253 formic acid Nutrition 0.000 claims abstract description 13
- 125000002252 acyl group Chemical group 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 239000004280 Sodium formate Substances 0.000 claims abstract description 8
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims abstract description 8
- 235000019254 sodium formate Nutrition 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 claims abstract description 4
- 229910052759 nickel Inorganic materials 0.000 claims abstract description 3
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 3
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 3
- 229910052794 bromium Inorganic materials 0.000 claims abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical group C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 13
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000013078 crystal Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- CJYWFYKAQKGDGP-UHFFFAOYSA-N dimethyl 3-(2-amino-6-chloropurin-9-yl)-2,2-dichlorocyclopropane-1,1-dicarboxylate Chemical compound ClC1(Cl)C(C(=O)OC)(C(=O)OC)C1N1C2=NC(N)=NC(Cl)=C2N=C1 CJYWFYKAQKGDGP-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910017053 inorganic salt Inorganic materials 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- RTNRLDYDDIWPQB-UHFFFAOYSA-N dimethyl 2-(2-aminopurin-9-yl)cyclopropane-1,1-dicarboxylate Chemical compound COC(=O)C1(C(=O)OC)CC1N1C2=NC(N)=NC=C2N=C1 RTNRLDYDDIWPQB-UHFFFAOYSA-N 0.000 description 2
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- UXFOSWFWQAUFFZ-UHFFFAOYSA-L barium(2+);diformate Chemical compound [Ba+2].[O-]C=O.[O-]C=O UXFOSWFWQAUFFZ-UHFFFAOYSA-L 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- OGSRAQBFMJYNFI-UHFFFAOYSA-N dimethyl 2-(2-amino-6-chloropurin-9-yl)cyclopropane-1,1-dicarboxylate Chemical compound COC(=O)C1(C(=O)OC)CC1N1C2=NC(N)=NC(Cl)=C2N=C1 OGSRAQBFMJYNFI-UHFFFAOYSA-N 0.000 description 1
- QMPLAWDUHSCQFG-UHFFFAOYSA-N dimethyl 3-(2-amino-6-methoxypurin-9-yl)-2,2-dichlorocyclopropane-1,1-dicarboxylate Chemical compound ClC1(Cl)C(C(=O)OC)(C(=O)OC)C1N1C2=NC(N)=NC(OC)=C2N=C1 QMPLAWDUHSCQFG-UHFFFAOYSA-N 0.000 description 1
- QVWSZHZOJVQMAW-UHFFFAOYSA-N dimethyl 3-(2-amino-6-phenylmethoxypurin-9-yl)-2,2-dichlorocyclopropane-1,1-dicarboxylate Chemical compound ClC1(Cl)C(C(=O)OC)(C(=O)OC)C1N1C2=NC(N)=NC(OCC=3C=CC=CC=3)=C2N=C1 QVWSZHZOJVQMAW-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、シクロプロパン環
開裂化合物の製造方法に関する。さらに詳しくは、抗ウ
イルス剤の製造中間体として有用なシクロプロパン環開
裂化合物の製造方法に関する。TECHNICAL FIELD The present invention relates to a method for producing a cyclopropane ring-cleaving compound. More specifically, the present invention relates to a method for producing a cyclopropane ring-cleaving compound useful as an intermediate for producing an antiviral agent.
【０００２】[0002]
【従来の技術】従来、シクロプロパン環開裂化合物は、
シクロプロパン環含有化合物に、金属触媒の存在下で、
水素源として水素ガスを作用させて水素添加し、還元的
に開裂することにより、製造する方法が知られている。2. Description of the Related Art Conventionally, cyclopropane ring-cleaving compounds have been
In a cyclopropane ring-containing compound, in the presence of a metal catalyst,
2. Description of the Related Art A production method is known in which a hydrogen gas is allowed to act as a hydrogen source, hydrogen is added, and reductive cleavage is performed.
【０００３】しかしながら、前記方法には、水素添加の
際に、反応系を３〜５ｋｇｆ／ｃｍ 2 程度に水素ガスで
加圧することが必要とされるため、作業性および安全性
に欠けることに加えて、副生成物が多いため、目的とす
るシクロプロパン環開裂化合物の収率が低いという欠点
がある。[0003] However, the above-mentioned method involves the addition of hydrogen.
At this time, the reaction system is 3 to 5 kgf / cm TwoAbout hydrogen gas
Workability and safety because pressure is required
In addition to lack of
Disadvantage of low yield of cyclopropane ring-cleaving compounds
There is.
【０００４】[0004]
【発明が解決しようとする課題】本発明は、前記従来技
術に鑑みてなされたものであり、作業性および安全性に
優れ、かつ高収率でシクロプロパン環開裂化合物を製造
する方法を提供することを目的とする。DISCLOSURE OF THE INVENTION The present invention has been made in view of the above prior art, and provides a method for producing a cyclopropane ring-cleaving compound which is excellent in workability and safety and in a high yield. The purpose is to:
【０００５】[0005]
【課題を解決するための手段】本発明の要旨は、式
（Ｉ）：The gist of the present invention is to provide a compound of the formula (I):
【０００６】[0006]
【化３】 Embedded image
【０００７】（式中、Ａは−ＣＨ2 −基または−ＣＯ−
基、Ｂは含窒素複素環、Ｘ1 およびＸ 2 は同一または異
なっていてもよい水素原子、塩素原子、臭素原子または
ヨウ素原子、Ｒ1 およびＲ2 は同一または異なっていて
もよい水素原子、炭素数１〜６のアルキル基または炭素
数１〜７でアシル基を示す。ただし、Ａが−ＣＯ−基で
あるとき、Ｒ1 およびＲ2 は、いずれも炭素数１〜７の
アシル基ではない）で表されるシクロプロパン環含有化
合物を触媒の存在下、ギ酸またはギ酸塩と反応させるこ
とを特徴とする式（II）：(Where A is -CHTwo-Group or -CO-
A group, B is a nitrogen-containing heterocyclic ring, X1And X TwoAre the same or different
Hydrogen atom, chlorine atom, bromine atom or
Iodine atom, R1And RTwoAre the same or different
Hydrogen atom, alkyl group having 1 to 6 carbon atoms or carbon atom
The acyl groups are represented by Formulas 1 to 7. Provided that A is a -CO- group
Once, R1And RTwoHas 1 to 7 carbon atoms
(Not an acyl group)
The compound is reacted with formic acid or formate in the presence of a catalyst.
Equation (II) characterized by:
【０００８】[0008]
【化４】 Embedded image
【０００９】（式中、Ａ、Ｂ、Ｒ1 およびＲ2 は前記と
同じ）で表されるシクロプロパン環開裂化合物の製造方
法に関する。(Wherein, A, B, R 1 and R 2 are the same as those described above).
【００１０】[0010]
【発明の実施の形態】本発明によれば、式（Ｉ）：According to the present invention, formula (I):
【００１１】[0011]
【化５】 Embedded image
【００１２】（式中、Ａは−ＣＨ2 −基または−ＣＯ−
基、Ｂは含窒素複素環、Ｘ1 およびＸ 2 は同一または異
なっていてもよい水素原子、塩素原子、臭素原子または
ヨウ素原子、Ｒ1 およびＲ2 は同一または異なっていて
もよい水素原子、炭素数１〜６のアルキル基または炭素
数１〜７でアシル基を示す。ただし、Ａが−ＣＯ−基で
あるとき、Ｒ1 およびＲ2 は、いずれも炭素数１〜７の
アシル基ではない）で表されるシクロプロパン環含有化
合物を触媒の存在下、ギ酸またはギ酸塩と反応させるこ
とにより、式（II）：(Where A is -CHTwo-Group or -CO-
A group, B is a nitrogen-containing heterocyclic ring, X1And X TwoAre the same or different
Hydrogen atom, chlorine atom, bromine atom or
Iodine atom, R1And RTwoAre the same or different
Hydrogen atom, alkyl group having 1 to 6 carbon atoms or carbon atom
The acyl groups are represented by Formulas 1 to 7. Provided that A is a -CO- group
Once, R1And RTwoHas 1 to 7 carbon atoms
(Not an acyl group)
The compound is reacted with formic acid or formate in the presence of a catalyst.
And with formula (II):
【００１３】[0013]
【化６】 Embedded image
【００１４】（式中、Ａ、Ｂ、Ｒ1 およびＲ2 は前記と
同じ）で表されるシクロプロパン環開裂化合物を製造す
ることができる。(Wherein A, B, R 1 and R 2 are the same as described above).
【００１５】式（Ｉ）で表される化合物において、Ａは
−ＣＨ2 −基または−ＣＯ−基である。In the compound represented by the formula (I), A is a —CH 2 — group or a —CO— group.
【００１６】Ｂは含窒素複素環を示す。本発明における
含窒素複素環としては、例えば、修飾または置換されて
いてもよい、プリン環、ピリミジン環などがあげられ
る。修飾または置換されていてもよい、プリン環および
ピリミジン環の代表例としては、例えば、その水素原子
が、ハロゲン原子、水酸基、炭素数１〜２０のアルキル
基、炭素数１〜２０のアルコキシ基、炭素数７〜２０の
アラルキルオキシ基および保護されていてもよいアミノ
基からなる群より選ばれた少なくとも１種の置換基で置
換されていてもよい、プリン環およびピリミジン環があ
げられる。ここで、炭素数１〜２０のアルキル基として
は、メチル基、エチル基、イソプロピル基などがあげら
れる。炭素数１〜２０のアルコキシ基としては、メトキ
シ基、エトキシ基、シクロヘキシルオキシ基、メンチル
オキシ基などがあげられる。炭素数７〜２０のアラルキ
ルオキシ基としては、ベンジルオキシ基、トリチルオキ
シ基などがあげられる。B represents a nitrogen-containing heterocyclic ring. Examples of the nitrogen-containing heterocycle in the present invention include a purine ring and a pyrimidine ring which may be modified or substituted. Representative examples of a purine ring and a pyrimidine ring which may be modified or substituted include, for example, a hydrogen atom having a halogen atom, a hydroxyl group, an alkyl group having 1 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, Examples include a purine ring and a pyrimidine ring which may be substituted with at least one substituent selected from the group consisting of an aralkyloxy group having 7 to 20 carbon atoms and an amino group which may be protected. Here, examples of the alkyl group having 1 to 20 carbon atoms include a methyl group, an ethyl group, and an isopropyl group. Examples of the alkoxy group having 1 to 20 carbon atoms include a methoxy group, an ethoxy group, a cyclohexyloxy group, and a menthyloxy group. Examples of the aralkyloxy group having 7 to 20 carbon atoms include a benzyloxy group and a trityloxy group.
【００１７】本発明において、前記修飾または置換され
ていてもよい、プリン環およびピリミジン環の具体例と
しては、例えば、２，４−ピリミジンジオニル基、４−
アミノ−２−ピリミジノニル基、５−メチル−２，４−
ピリミジンジオニル基、２−アミノプリニル基、６−ア
ミノプリニル基、２−アミノ−６−ヒドロキシプリニル
基、２，６−ジアミノプリニル基、２−アミノ−６−ク
ロロプリニル基、２−アミノ−６−ヨードプリニル基、
２−アミノ−６−メトキシプリニル基、２−アミノ−６
−ベンジルオキシプリニル基、２，６−ジクロロプリニ
ル基などがあげられる。In the present invention, specific examples of the aforementioned modified or substituted purine ring and pyrimidine ring include, for example, a 2,4-pyrimidinedionyl group,
Amino-2-pyrimidinonyl group, 5-methyl-2,4-
Pyrimidinedionyl group, 2-aminoprinyl group, 6-aminopurinyl group, 2-amino-6-hydroxypurinyl group, 2,6-diaminopurinyl group, 2-amino-6-chloropurinyl group, 2-amino-6- Iodopurinyl group,
2-amino-6-methoxypurinyl group, 2-amino-6
-Benzyloxypurinyl group, 2,6-dichloropurinyl group and the like.
【００１８】Ｘ1 およびＸ2 は同一または異なっていて
もよい水素原子、塩素原子、臭素原子またはヨウ素原子
を示す。X 1 and X 2 represent a hydrogen atom, a chlorine atom, a bromine atom or an iodine atom which may be the same or different.
【００１９】Ｒ1 およびＲ2 は同一または異なっていて
もよい水素原子、炭素数１〜６のアルキル基または炭素
数１〜７のアシル基を示す。R 1 and R 2 represent a hydrogen atom which may be the same or different, an alkyl group having 1 to 6 carbon atoms or an acyl group having 1 to 7 carbon atoms.
【００２０】前記炭素数１〜６のアルキル基の代表例と
しては、メチル基、エチル基、プロピル基、イソプロピ
ル基などがあげられる。Representative examples of the alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, a propyl group and an isopropyl group.
【００２１】前記炭素数１〜７のアシル基としては、例
えば、ホルミル基、アセチル基、プロピオニル基、ピバ
ロイル基、ベンゾイル基などがあげられる。ただし、Ａ
が−ＣＯ−基であるとき、Ｒ1 およびＲ2 は、いずれも
炭素数１〜７のアシル基はない。Examples of the acyl group having 1 to 7 carbon atoms include a formyl group, an acetyl group, a propionyl group, a pivaloyl group and a benzoyl group. However, A
Is a -CO- group, none of R 1 and R 2 has an acyl group having 1 to 7 carbon atoms.
【００２２】式（Ｉ）で表されるシクロプロパン環含有
化合物の代表例としては、例えば、２−アミノ−６−ク
ロロ−９−（２，２−ジクロロ−３，３−ジカルボメト
キシシクロプロピル）プリン、２−アミノ−９−（３，
３−ジカルボメトキシシクロプロピル）プリン、２−ア
ミノ−６−クロロ−９−（３，３−ジカルボメトキシシ
クロプロピル）プリン、２−アミノ−９−（２，２−ジ
クロロ−３，３−ジカルボメトキシシクロプロピル）−
６−メトキシプリン、２−アミノ−６−ベンジルオキシ
−９−（２，２−ジクロロ−３，３−ジカルボメトキシ
シクロプロピル）プリンなどがあげられる。Typical examples of the cyclopropane ring-containing compound represented by the formula (I) include, for example, 2-amino-6-chloro-9- (2,2-dichloro-3,3-dicarbomethoxycyclopropyl ) Purine, 2-amino-9- (3,
3-dicarbomethoxycyclopropyl) purine, 2-amino-6-chloro-9- (3,3-dicarbomethoxycyclopropyl) purine, 2-amino-9- (2,2-dichloro-3,3- Dicarbomethoxycyclopropyl)-
6-methoxypurine, 2-amino-6-benzyloxy-9- (2,2-dichloro-3,3-dicarbomethoxycyclopropyl) purine and the like.
【００２３】式（Ｉ）で表されるシクロプロパン環含有
化合物は、例えば、特開平３−１２０２７９号公報、特
願平９−３１０８３９号明細書などに記載の方法により
得ることができる。The cyclopropane ring-containing compound represented by the formula (I) can be obtained, for example, by the methods described in JP-A-3-120279 and Japanese Patent Application No. 9-310839.
【００２４】本発明において、前記式（Ｉ）で表される
シクロプロパン環含有化合物と、ギ酸またはギ酸塩との
反応は、例えば、式（Ｉ）で表されるシクロプロパン環
含有化合物および触媒を、溶媒に添加した後、ギ酸また
はギ酸塩を添加することにより、行なうことができる。In the present invention, the reaction between the cyclopropane ring-containing compound represented by the formula (I) and formic acid or formate is carried out, for example, by reacting the cyclopropane ring-containing compound represented by the formula (I) and a catalyst. , A solvent, and then adding formic acid or a formate.
【００２５】触媒としては、パラジウム、白金、ニッケ
ル、それらの化合物などがあげられ、これらは単独で用
いてもよく、２種以上を混合して用いてもよい。前記そ
れらの化合物としては、例えば、水酸化パラジウムなど
の水酸化物、酸化白金などの酸化物、ラネーニッケルな
どの展開触媒、パラジウム黒、白金黒などの金属状触媒
などがあげられる。また、前記触媒は、そのままの状態
で使用してもよく、パラジウム炭素のように、炭素など
に担持させた担持触媒として用いてもよい。これらの中
では、汎用性及び反応性の観点から、パラジウム炭素、
白金炭素、パラジウム黒、水酸化パラジウムおよびラネ
ーニッケルが好ましい。Examples of the catalyst include palladium, platinum, nickel, and compounds thereof. These may be used alone or as a mixture of two or more. Examples of such compounds include hydroxides such as palladium hydroxide, oxides such as platinum oxide, developing catalysts such as Raney nickel, and metallic catalysts such as palladium black and platinum black. The catalyst may be used as it is, or may be used as a supported catalyst supported on carbon or the like, such as palladium carbon. Among these, from the viewpoint of versatility and reactivity, palladium carbon,
Platinum carbon, palladium black, palladium hydroxide and Raney nickel are preferred.
【００２６】触媒の使用量は、式（Ｉ）で表されるシク
ロプロパン環含有化合物１００重量部に対して、通常、
反応を速やかに進行させるため、０．１重量部以上、好
ましくは１０重量部以上であることが望ましく、経済性
の観点から、１００重量部以下、好ましくは５０重量部
以下であることが望ましい。The amount of the catalyst to be used is usually based on 100 parts by weight of the cyclopropane ring-containing compound represented by the formula (I).
In order to allow the reaction to proceed promptly, the amount is preferably 0.1 part by weight or more, preferably 10 parts by weight or more, and from the viewpoint of economy, it is preferably 100 parts by weight or less, preferably 50 parts by weight or less.
【００２７】溶媒としては、特に限定されないが、例え
ば、水、メタノール、エタノール、イソプロパノールな
どのアルコール類、テトラヒドロフランなどのエーテル
類、酢酸エチルなどのエステル類、ジメチルホルムアミ
ドなどの極性溶媒などがあげられ、これらは単独でまた
は２種以上を混合して用いることができる。該溶媒の使
用量は、溶媒１００重量部に対して、式（Ｉ）で表され
るシクロプロパン環含有化合物が１〜５０重量部程度と
なるように、調整することが好ましい。The solvent is not particularly restricted but includes, for example, water, alcohols such as methanol, ethanol and isopropanol, ethers such as tetrahydrofuran, esters such as ethyl acetate, and polar solvents such as dimethylformamide. These can be used alone or in combination of two or more. The amount of the solvent used is preferably adjusted so that the amount of the cyclopropane ring-containing compound represented by the formula (I) is about 1 to 50 parts by weight based on 100 parts by weight of the solvent.
【００２８】本発明においては、ギ酸またはギ酸塩を用
いる点に、１つの大きな特徴がある。かかるギ酸または
ギ酸塩を用いた場合には、従来のように水素ガスで反応
系を加圧する必要がなく、式（Ｉ）で表されるシクロプ
ロパン環含有化合物を効率よく水素添加させ、高収率で
式（II）で表されるシクロプロパン環開裂化合物を作業
性よく、しかも安全に得ることができる、という優れた
効果が発現される。The use of formic acid or formate in the present invention has one significant feature. When such formic acid or formate is used, it is not necessary to pressurize the reaction system with hydrogen gas as in the prior art, and the cyclopropane ring-containing compound represented by the formula (I) can be efficiently hydrogenated to obtain a high yield. An excellent effect that the cyclopropane ring-cleaving compound represented by the formula (II) can be obtained with good workability and safety at a high rate.
【００２９】ギ酸塩としては、ギ酸ナトリウム、ギ酸カ
リウム、ギ酸アンモニウム、ギ酸バリウム、ギ酸トリエ
チルアンモニウムなどがあげられる。これらのなかで
は、経済性および作業性の観点から、ギ酸ナトリウム、
ギ酸カリウムおよびギ酸アンモニウムが好ましい。Examples of the formate include sodium formate, potassium formate, ammonium formate, barium formate and triethylammonium formate. Among them, sodium formate,
Potassium and ammonium formate are preferred.
【００３０】ギ酸またはギ酸塩の使用量は、式（Ｉ）で
表されるシクロプロパン環含有化合物１モルに対して、
反応を完結させるため、１モル以上、好ましくは１．５
モル以上であることが望ましく、経済性の観点から、２
０モル以下、好ましくは１０モル以下であることが望ま
しい。The amount of formic acid or formate used is based on 1 mole of the cyclopropane ring-containing compound represented by the formula (I).
In order to complete the reaction, at least 1 mol, preferably 1.5 mol
Mol or more, and from the viewpoint of economy, 2
It is desirably 0 mol or less, preferably 10 mol or less.
【００３１】本発明において、式（Ｉ）で表されるシク
ロプロパン環含有化合物と、ギ酸またはギ酸塩との反応
は、前記したように、特に反応系を加圧する必要がな
く、常圧下で行なうことができる。In the present invention, the reaction between the cyclopropane ring-containing compound represented by the formula (I) and formic acid or formate is carried out at normal pressure without the need to pressurize the reaction system as described above. be able to.
【００３２】式（Ｉ）で表されるシクロプロパン環含有
化合物と、ギ酸またはギ酸塩との反応を行なう際の反応
温度は、通常、０〜１５０℃、好ましくは２０〜８０℃
であることが望ましい。また、反応の際の雰囲気は、特
に限定されないが、不活性ガス雰囲気下または水素ガス
雰囲気下であることが好ましい。The reaction temperature at the time of reacting the cyclopropane ring-containing compound represented by the formula (I) with formic acid or formate is usually 0 to 150 ° C, preferably 20 to 80 ° C.
It is desirable that The atmosphere during the reaction is not particularly limited, but is preferably under an inert gas atmosphere or a hydrogen gas atmosphere.
【００３３】反応時間は、反応温度などの反応条件によ
って異なるので一概には決定することができないが、反
応が終了する程度の時間であればよく、通常、１〜１０
時間程度であることが好ましい。反応の終了の確認は、
例えば、高速液体クロマトグラフィーを用いて原料物質
の消失を確認することにより、行うことができる。The reaction time varies depending on the reaction conditions such as the reaction temperature, and cannot be unconditionally determined. However, the reaction time may be such that the reaction is completed.
Preferably, it is about an hour. To confirm the end of the reaction,
For example, it can be carried out by confirming the disappearance of the raw material using high performance liquid chromatography.
【００３４】反応終了後、得られた反応混合物には、本
発明における目的化合物である式(II)で表されるシクロ
プロパン環開裂化合物のほか、析出した無機塩が含まれ
ている。したがって、例えば、反応混合物から触媒等を
濾過により取り除いた後、得られた濾液を濃縮し、目的
化合物を溶解する溶媒、例えば、テトラヒドロフラン等
に懸濁し、不溶物を濾過することにより、得られた反応
混合物から該無機塩を除去することができる。After completion of the reaction, the obtained reaction mixture contains the cyclopropane ring-cleaving compound represented by the formula (II), which is the target compound of the present invention, and the precipitated inorganic salt. Therefore, for example, after removing the catalyst and the like from the reaction mixture by filtration, the obtained filtrate is concentrated, the target compound is dissolved in a solvent, for example, suspended in tetrahydrofuran or the like, and insolubles are obtained by filtration. The inorganic salt can be removed from the reaction mixture.
【００３５】さらに、得られた式(II)で表されるシクロ
プロパン環開裂化合物は、必要により、例えば、２−プ
ロパノールなどを用いて再結晶することができる。Further, the obtained cyclopropane ring-cleaving compound represented by the formula (II) can be recrystallized by using, for example, 2-propanol, if necessary.
【００３６】このようにして得られる式(II)で表される
シクロプロパン環開裂化合物は、例えば、ヌクレオシド
・ヌクレオチド（Nucleoside Nucleotide), 15〔５〕(1
996)，p. 981-994、特公平５−８６７９２号公報等に記
載されている抗ウイルス剤の有用な中間体を、効率よく
製造するのに好適に使用しうる化合物である。The cyclopropane ring-cleaving compound represented by the formula (II) thus obtained is, for example, a nucleoside nucleotide (Nucleoside Nucleotide), 15 [5] (1
996), p. 981-994, JP-B 5-86792, and the like, and are compounds that can be suitably used for efficiently producing useful intermediates for antiviral agents.
【００３７】[0037]
【実施例】次に、本発明を実施例に基づいてさらに詳細
に説明するが、本発明はかかる実施例のみに限定される
ものではない。Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to only these examples.
【００３８】実施例１ ２−アミノ−６−クロロ−９−（２，２−ジクロロ−
３，３−ジカルボメトキシシクロプロピル）プリン１３
９．０ｇ（３５２．２ミリモル）と、１０％パラジウム
炭素（５０％ウェット品、川研ファインケミカル（株）
製）１３９．０ｇとをメタノール２７８０ｍｌに添加
し、続いて、これにギ酸ナトリウム１３５．２ｇ（１９
８８ミリモル）を添加した。５５〜６１℃で７時間反応
させた後、反応混合物を濾過した。濾液を減圧下に濃縮
し、テトラヒドロフラン２４００ｍｌに懸濁させた。不
溶の無機塩を濾別し、濾液を濃縮乾固して白色結晶を得
た。得られた白色結晶を２−プロパノール２１０ｍｌか
ら再結晶し、２−（２−（２−アミノプリン−９−イ
ル）エチル）マロン酸ジメチルの白色結晶９３．０ｇ
（３１７．０ミリモル）を得た（収率：９０．０％）。
得られた結晶を高速液体クロマトグラフィーで分析した
ところ、純度は９９．０％であった。Example 1 2-amino-6-chloro-9- (2,2-dichloro-
3,3-dicarbomethoxycyclopropyl) purine 13
9.0 g (352.2 mmol) and 10% palladium carbon (50% wet product, Kawaken Fine Chemical Co., Ltd.)
Was added to 2780 ml of methanol, and 135.2 g of sodium formate (199.0 g) was added thereto.
(88 mmol). After reacting at 55-61 ° C for 7 hours, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure and suspended in 2,400 ml of tetrahydrofuran. The insoluble inorganic salt was separated by filtration, and the filtrate was concentrated to dryness to obtain white crystals. The obtained white crystals were recrystallized from 210 ml of 2-propanol to give 93.0 g of white crystals of dimethyl 2- (2- (2-aminopurin-9-yl) ethyl) malonate.
(317.0 mmol) was obtained (yield: 90.0%).
When the obtained crystals were analyzed by high performance liquid chromatography, the purity was 99.0%.
【００３９】得られた結晶が２−（２−（２−アミノプ
リン−９−イル）エチル）マロン酸ジメチルであること
は、以下の物性により確認された。 （１） 融点：１１１〜１１２℃（文献値：１１０〜１
１２℃） （２） 1Ｈ−ＮＭＲ（２７０ＭＨｚ，ＤＭＳＯ−
ｄ6 ）δ：８．５４（ｓ，１Ｈ）、７．９８（ｓ，１
Ｈ）、６．４５（ｂｒｓ，２Ｈ）、４．１０（ｔ，３
Ｈ）、３．５８（ｓ，６Ｈ）、３．４９（ｔ，１Ｈ）、
２．３２（ｑ，２Ｈ） （３） 13Ｃ−ＮＭＲ（６７．５ＭＨｚ，ＤＭＳＯ−ｄ
6 ）δ：１６８．７、１６０．４、１５２．９、１４
８．９、１４２．５、１２６．８、５２．４、４８．４It was confirmed by the following physical properties that the obtained crystal was dimethyl 2- (2- (2-aminopurin-9-yl) ethyl) malonate. (1) Melting point: 111-112 ° C (literature value: 110-1)
(12 ° C) (2) 1 H-NMR (270 MHz, DMSO-
d 6 ) δ: 8.54 (s, 1H), 7.98 (s, 1)
H), 6.45 (brs, 2H), 4.10 (t, 3
H), 3.58 (s, 6H), 3.49 (t, 1H),
2.32 (q, 2H) (3) 13 C-NMR (67.5 MHz, DMSO-d
6 ) δ: 168.7, 160.4, 152.9, 14
8.9, 142.5, 126.8, 52.4, 48.4
【００４０】実施例２ 実施例１において、ギ酸ナトリウムのかわりにギ酸アン
モニウム１２５．３ｇ（１９８８ミリモル）を使用した
以外は実施例１と同様の操作をし、実施例１で得られた
白色結晶と同様の物性を有する、２−（２−（２−アミ
ノプリン−９−イル）エチル）マロン酸ジメチルの白色
結晶９２．０ｇ（３１３．７ミリモル）を得た（収率：
８９．０％）。得られた結晶を高速液体クロマトグラフ
ィーで分析したところ、純度は９８．９％であった。Example 2 The same procedure as in Example 1 was carried out except that 125.3 g (1988 mmol) of ammonium formate was used instead of sodium formate, and the white crystals obtained in Example 1 were used. 92.0 g (313.7 mmol) of white crystals of dimethyl 2- (2- (2-aminopurin-9-yl) ethyl) malonate having similar physical properties were obtained (yield:
89.0%). When the obtained crystals were analyzed by high performance liquid chromatography, the purity was 98.9%.
【００４１】実施例３ 実施例１において、ギ酸ナトリウムのかわりにギ酸カリ
ウム１６７．２ｇ（１９８８ミリモル）を使用した以外
は実施例１と同様の操作をし、実施例１で得られた白色
結晶と同様の物性を有する、２−（２−（２−アミノプ
リン−９−イル）エチル）マロン酸ジメチルの白色結晶
９０．９ｇ（３０９．９ミリモル）を得た（収率：８
８．０％）。得られた結晶を高速液体クロマトグラフィ
ーで分析したところ、純度は９９．０％であった。Example 3 The same procedure as in Example 1 was carried out except that 167.2 g (1988 mmol) of potassium formate was used instead of sodium formate, and the white crystal obtained in Example 1 was replaced with the white crystal obtained in Example 1. 90.9 g (309.9 mmol) of white crystals of dimethyl 2- (2- (2-aminopurin-9-yl) ethyl) malonate having similar properties were obtained (yield: 8).
8.0%). When the obtained crystals were analyzed by high performance liquid chromatography, the purity was 99.0%.
【００４２】実施例４ 実施例１において、２−アミノ−６−クロロ−９−
（２，２−ジクロロ−３，３−ジカルボメトキシシクロ
プロピル）プリンのかわりに２−アミノ−９−（３，３
−ジカルボメトキシシクロプロピル）プリン１０２．６
ｇ（３５２．２ミリモル）を、ギ酸ナトリウムのかわり
に９８％ギ酸２４．８ｇ（５２８．４ミリモル）を使用
した以外は実施例１と同様の操作をし、２−（２−（２
−アミノプリン−９−イル）エチル）マロン酸ジメチル
の白色結晶９０．５ｇ（３０８．６ミリモル）を得た
（収率：８７．６％）。得られた結晶を高速液体クロマ
トグラフィーで分析したところ、純度は９９．０％であ
った。Example 4 In Example 1, 2-amino-6-chloro-9-
Instead of (2,2-dichloro-3,3-dicarbomethoxycyclopropyl) purine, 2-amino-9- (3,3
-Dicarbomethoxycyclopropyl) purine 102.6
g (352.2 mmol) was replaced with 2-4.8 g (528.4 mmol) of 98% formic acid in place of sodium formate, and the same operation as in Example 1 was carried out to give 2- (2- (2
90.5 g (308.6 mmol) of white crystals of -aminopurin-9-yl) ethyl) dimethyl malonate were obtained (yield: 87.6%). When the obtained crystals were analyzed by high performance liquid chromatography, the purity was 99.0%.
【００４３】比較例１ ２−アミノ−６−クロロ−９−（２，２−ジクロロ−
３，３−ジカルボメトキシシクロプロピル）プリン５．
０ｇ（１２．６ミリモル）と５％パラジウム炭素５．０
ｇをメタノール７５ｍｌに添加した後、９０℃で約５ｋ
ｇｆ／ｃｍ2 の水素加圧条件下で約５時間反応を行っ
た。反応混合物液を濾過し、減圧下で濃縮した。残渣に
水１０ｍｌと酢酸エチル７５ｍｌを加えた後、３０分間
攪拌し、酢酸エチル層を分取し、カラムクロマトグラフ
ィーにより精製し、２−（２−（２−アミノプリン−９
−イル）エチル）マロン酸ジメチルの白色結晶１．８ｇ
（６．３ミリモル）を得た（収率：５０．０％）。得ら
れた結晶を高速液体クロマトグラフィーで分析したとこ
ろ、純度は９８．８％であった。Comparative Example 1 2-amino-6-chloro-9- (2,2-dichloro-
3,3-dicarbomethoxycyclopropyl) purine
0 g (12.6 mmol) and 5% palladium on carbon 5.0
g was added to 75 ml of methanol.
The reaction was carried out under a hydrogen pressure of gf / cm 2 for about 5 hours. The reaction mixture was filtered and concentrated under reduced pressure. After adding 10 ml of water and 75 ml of ethyl acetate to the residue, the mixture was stirred for 30 minutes, the ethyl acetate layer was separated, and purified by column chromatography to give 2- (2- (2-aminopurine-9).
1.8 g of white crystals of -yl) ethyl) dimethyl malonate
(6.3 mmol) was obtained (yield: 50.0%). When the obtained crystals were analyzed by high performance liquid chromatography, the purity was 98.8%.
【００４４】以上の結果から、実施例１〜４の方法によ
れば、従来の比較例１のように、水素ガスで反応系を加
圧するという安全性が懸念されている操作を用いなくて
も、シクロプロパン環開裂化合物を高収率で得ることが
できることがわかる。From the above results, according to the methods of Examples 1 to 4, unlike the conventional Comparative Example 1, the operation of pressurizing the reaction system with hydrogen gas, which is concerned with safety, is not required. It can be seen that a cyclopropane ring-cleaving compound can be obtained in high yield.
【００４５】[0045]
【発明の効果】本発明によれば、式（II）で表されるシ
クロプロパン環開裂化合物を、作業性よく、しかも安全
に、高収率で製造することができるという優れた効果が
奏される。According to the present invention, there is provided an excellent effect that the cyclopropane ring-cleaving compound represented by the formula (II) can be produced with good workability, safely and in a high yield. You.
Claims (3)
素複素環、Ｘ1 およびＸ 2 は同一または異なっていても
よい水素原子、塩素原子、臭素原子またはヨウ素原子、
Ｒ1 およびＲ2 は同一または異なっていてもよい水素原
子、炭素数１〜６のアルキル基または炭素数１〜７でア
シル基を示す。ただし、Ａが−ＣＯ−基であるとき、Ｒ
1 およびＲ2 は、いずれも炭素数１〜７のアシル基では
ない）で表されるシクロプロパン環含有化合物を触媒の
存在下、ギ酸またはギ酸塩と反応させることを特徴とす
る式（II）： 【化２】 （式中、Ａ、Ｂ、Ｒ1 およびＲ2 は前記と同じ）で表さ
れるシクロプロパン環開裂化合物の製造方法。1. A compound of formula (I):(Wherein A is -CHTwo-Group or -CO- group, B is nitrogen-containing
Prime heterocycle, X1And X TwoAre the same or different
Good hydrogen, chlorine, bromine or iodine,
R1And RTwoIs a hydrogen source which may be the same or different
An alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 7 carbon atoms.
Represents a sil group. Provided that when A is a -CO- group,
1And RTwoIs an acyl group having 1 to 7 carbon atoms
The compound containing a cyclopropane ring represented by
Reacting with formic acid or formate in the presence
Formula (II):(Where A, B, R1And RTwoIs the same as above)
For producing a cyclopropane ring-cleaving compound.
それらの化合物からなる群より選ばれた少なくとも１種
である請求項１記載のシクロプロパン環開裂化合物の製
造方法。2. The method according to claim 1, wherein the catalyst is at least one selected from the group consisting of palladium, platinum, nickel and compounds thereof.
またはギ酸アンモニウムである請求項１または２記載の
シクロプロパン環開裂化合物の製造方法。3. The method for producing a cyclopropane ring-cleaving compound according to claim 1, wherein the formate is sodium formate, potassium formate or ammonium formate.
Priority Applications (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10133349A JPH11322749A (en) | 1998-05-15 | 1998-05-15 | Production of opened cyclopropane ring compound |
| CA002251481A CA2251481A1 (en) | 1997-11-12 | 1998-10-26 | Purine derivatives having cyclopropane ring |
| AU89553/98A AU737518B2 (en) | 1997-11-12 | 1998-10-28 | Purine derivatives having cyclopropane ring |
| US09/184,747 US6156892A (en) | 1997-11-12 | 1998-11-03 | Purine derivatives having cyclopropane ring |
| DK98309170T DK0916674T3 (en) | 1997-11-12 | 1998-11-10 | Cyclopropane ring-containing purine derivatives |
| PT98309170T PT916674E (en) | 1997-11-12 | 1998-11-10 | PURINA DERIVATIVES WITH A CYCLOPROPANE RING. |
| ES98309170T ES2176914T3 (en) | 1997-11-12 | 1998-11-10 | DERIVED FROM THE PURINE THAT HAVE A CYCLOPROPAN RING. |
| EP98309170A EP0916674B1 (en) | 1997-11-12 | 1998-11-10 | Purine derivatives having cyclopropane ring |
| KR1019980047991A KR19990045165A (en) | 1997-11-12 | 1998-11-10 | A purine derivative containing a cyclopropane ring |
| DE69805267T DE69805267T2 (en) | 1997-11-12 | 1998-11-10 | Purine derivatives containing cyclopropancyclus |
| AT98309170T ATE217311T1 (en) | 1997-11-12 | 1998-11-10 | PURINE DERIVATIVES CONTAINING CYCLOPROPANCYCLUS |
| ARP990102174 AR018343A1 (en) | 1998-05-15 | 1999-05-07 | PURINIC DERIVATIVE THAT HAS A CYCLOPROPANE RING, PROCEDURE TO PREPARE IT AND PROCEDURE TO PREPARE A PURINIC DERIVATIVE BY BREAKING A CYCLOPROPAN UNANILO FROM THE SAME |
| BR9901429A BR9901429A (en) | 1998-05-15 | 1999-05-11 | Purine derivatives having cyclopropane ring |
| US09/541,724 US6342603B1 (en) | 1997-11-12 | 2000-04-03 | Purine derivatives having cyclopropane ring |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10133349A JPH11322749A (en) | 1998-05-15 | 1998-05-15 | Production of opened cyclopropane ring compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11322749A true JPH11322749A (en) | 1999-11-24 |
Family
ID=15102653
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10133349A Pending JPH11322749A (en) | 1997-11-12 | 1998-05-15 | Production of opened cyclopropane ring compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11322749A (en) |
-
1998
- 1998-05-15 JP JP10133349A patent/JPH11322749A/en active Pending
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