JPS6152828B2 - - Google Patents
Info
- Publication number
- JPS6152828B2 JPS6152828B2 JP54079136A JP7913679A JPS6152828B2 JP S6152828 B2 JPS6152828 B2 JP S6152828B2 JP 54079136 A JP54079136 A JP 54079136A JP 7913679 A JP7913679 A JP 7913679A JP S6152828 B2 JPS6152828 B2 JP S6152828B2
- Authority
- JP
- Japan
- Prior art keywords
- ribofuranose
- acid
- deoxy
- alkali salt
- phosphate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000002253 acid Substances 0.000 claims description 13
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 12
- TWGNOYAGHYUFFR-UHFFFAOYSA-N 5-methylpyrimidine Chemical class CC1=CN=CN=C1 TWGNOYAGHYUFFR-UHFFFAOYSA-N 0.000 claims description 11
- 229910052751 metal Inorganic materials 0.000 claims description 11
- 239000002184 metal Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 150000001447 alkali salts Chemical class 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 230000027756 respiratory electron transport chain Effects 0.000 claims description 6
- 229910052739 hydrogen Chemical group 0.000 claims description 5
- 239000001257 hydrogen Chemical group 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 5
- 229940071870 hydroiodic acid Drugs 0.000 claims description 5
- 150000002972 pentoses Chemical group 0.000 claims description 5
- TYRDEZUMAVRTEO-UHFFFAOYSA-N pyrimidin-5-ylmethanol Chemical class OCC1=CN=CN=C1 TYRDEZUMAVRTEO-UHFFFAOYSA-N 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- -1 pentose phosphate Chemical group 0.000 claims description 4
- ZUYIBYOYYUXIGY-VPENINKCSA-N (2r,3r,5s)-5-(hydroxymethyl)oxolane-2,3-diol Chemical compound OC[C@@H]1C[C@@H](O)[C@H](O)O1 ZUYIBYOYYUXIGY-VPENINKCSA-N 0.000 claims description 3
- PDWIQYODPROSQH-VPENINKCSA-N (2r,4s,5r)-5-(hydroxymethyl)oxolane-2,4-diol Chemical compound OC[C@H]1O[C@@H](O)C[C@@H]1O PDWIQYODPROSQH-VPENINKCSA-N 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- KTVPXOYAKDPRHY-TXICZTDVSA-N 5-O-phosphono-beta-D-ribofuranose Chemical compound O[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O KTVPXOYAKDPRHY-TXICZTDVSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 3
- HMFHBZSHGGEWLO-SQOUGZDYSA-N beta-D-arabinofuranose Chemical compound OC[C@H]1O[C@@H](O)[C@@H](O)[C@@H]1O HMFHBZSHGGEWLO-SQOUGZDYSA-N 0.000 claims description 3
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 claims description 3
- HMFHBZSHGGEWLO-KKQCNMDGSA-N beta-D-xylofuranose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@H]1O HMFHBZSHGGEWLO-KKQCNMDGSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229910052718 tin Inorganic materials 0.000 claims description 2
- KKZFLSZAWCYPOC-VPENINKCSA-N Deoxyribose 5-phosphate Chemical compound O[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 KKZFLSZAWCYPOC-VPENINKCSA-N 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000000243 solution Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000007788 liquid Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 8
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000000862 absorption spectrum Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000010531 catalytic reduction reaction Methods 0.000 description 3
- 239000003729 cation exchange resin Substances 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- PTJWIQPHWPFNBW-JWXFUTCRSA-N 5-[(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-JWXFUTCRSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- DWRXFEITVBNRMK-JAGXHNFQSA-N Spongothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JAGXHNFQSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 229910001507 metal halide Inorganic materials 0.000 description 1
- 150000005309 metal halides Chemical class 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- ZPEJZWGMHAKWNL-UHFFFAOYSA-L zinc;oxalate Chemical compound [Zn+2].[O-]C(=O)C([O-])=O ZPEJZWGMHAKWNL-UHFFFAOYSA-L 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Saccharide Compounds (AREA)
Description
【発明の詳細な説明】
本発明は５−メチルピリミジン誘導体の新規な
製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 5-methylpyrimidine derivatives.
本発明方法によつて製造される化合物群は、医
薬および生化学研究用試薬として、またその製造
中間体として重要であり、本発明はこれらの物質
の経済的で効率的な製造法を提供するものであ
る。本発明の化合物群中、特にチミジンは、メソ
トレキセート、フルオロデオキシウリジン、５−
フルオロウラシルなどの抗腫瘍剤の副作用を軽減
する作用が知られており（例えば、アナルス・オ
ブ・ザ・ニユーヨーク・アカデミー・オブ・サイ
エンス（Ann.N.Y.Acad.Sci.）第255巻、第261〜
265頁、1975年参照）、また、近年、チミジン自体
の大量投与によつて腫瘍の増殖を抑える効果があ
ることも報告され（キヤンサー・レターズ
（Cancer Letters）第３巻、第209〜214頁、1977
年参照）、その重要度が増しつつある。また、１
−β−Ｄ−アルビノフラノシルチミン（アラＴ）
は抗ウイルス活性を持つことが知られており、そ
の医薬としての用途が期待されている。一方、１
−β−Ｄ−リボフラノシルチミンは前記物質の合
成中間体として重要である。 The compounds produced by the method of the present invention are important as reagents for pharmaceutical and biochemical research, and as intermediates for their production, and the present invention provides an economical and efficient method for producing these substances. It is something. Among the compounds of the present invention, thymidine is particularly suitable for methotrexate, fluorodeoxyuridine, 5-
It is known to reduce the side effects of antitumor drugs such as fluorouracil (for example, Ann. NYAcad. Sci., Vol. 255, No. 261-).
265, 1975), and in recent years, it has also been reported that large doses of thymidine itself have the effect of suppressing tumor growth (Cancer Letters, Vol. 3, pp. 209-214). 1977
), its importance is increasing. Also, 1
-β-D-Albinofuranosylthymine (AraT)
is known to have antiviral activity and is expected to be used as a medicine. On the other hand, 1
-β-D-ribofuranosylthymine is important as a synthetic intermediate for the above substances.
従来、５−ハイドロキシメチルピリミジン化合
物のハイドロキシメチル基のメチル基への還元方
法としては接触還元法が一般的であつた（ザ・ジ
ヤーナル・オブ・ジ・アメリカン・ケミカル・ソ
サイエテイ（J.Am.Chem.Soc.）第81巻、第2521
〜2527頁、1959年参照）。しかしながら、この方
法には、使用する触媒（酸化白金など）が高価で
ある。中圧接触還元装置などの特別な設備を必要
とする、など工業的製造に際して不利な面があ
る。 Conventionally, a catalytic reduction method has been common as a method for reducing the hydroxymethyl group of 5-hydroxymethylpyrimidine compounds to a methyl group (The Journal of the American Chemical Society (J.Am.Chem. .Soc.) Volume 81, No. 2521
~2527 pages, 1959). However, this method requires expensive catalysts (such as platinum oxide). There are disadvantages in industrial production, such as the need for special equipment such as a medium-pressure catalytic reduction device.
本発明者は前記の欠点を克服し、工業的に適用
可能な５−メチルピリミジン誘導体の製造法を確
立すべく、種々検討した結果、５−ハイドロキシ
メチルピリミジン誘導体を原料とし、該物質をハ
ロゲン化水素酸存在下に電子移動による還元能を
有する金属と反応させることにより、高価な触
媒、接触還元装置などを使用することなく５−メ
チルピリミジン誘導体が得られることを見出し、
本発明を完成した。 In order to overcome the above-mentioned drawbacks and establish an industrially applicable manufacturing method for 5-methylpyrimidine derivatives, the present inventor conducted various studies, and found that using 5-hydroxymethylpyrimidine derivatives as a raw material, halogenation of the substance We have discovered that 5-methylpyrimidine derivatives can be obtained without using expensive catalysts, catalytic reduction equipment, etc. by reacting them with metals that have the ability to reduce by electron transfer in the presence of hydrogen acid,
The invention has been completed.
本発明は、一般式〔〕
で表わされる５−ハイドロキシメチルピリミジン
誘導体をハロゲン化水素酸存在下、電子移動によ
る還元能を有する金属と反応せしめ、５位ハイド
ロキシメチル基をメチル基に還元して一般式
〔〕
で表わされる５−メチルピリミジン誘導体を得る
方法である。 The present invention is based on the general formula [] A 5-hydroxymethylpyrimidine derivative represented by the formula is reacted with a metal capable of reducing through electron transfer in the presence of hydrohalic acid, and the 5-hydroxymethyl group is reduced to a methyl group to form the general formula [] This is a method for obtaining a 5-methylpyrimidine derivative represented by
上記一般式〔〕および〔〕において、Ｒは
保護基を有することもあるペントース、ペントー
スりん酸または水素を示す。具体的には、保護基
を有しないペントースの代表例としては、β−Ｄ
−リボフラノース、２−デオキシ−β−Ｄ−リボ
フラノース、３−デオキシ−β−Ｄ−リボフラノ
ース、β−Ｄ−アラビノフラノース、β−Ｄ−キ
シロフラノースなどが挙げられる。保護基を有す
るペントースの代表例としては、２・３−Ｏ−ア
ルキリデンまたはアルアルキリデン−β−Ｄ−リ
ボフラノース、３・５−Ｏ−アルキリデンまたは
アルアルキリデン−β−Ｄ−キシロフラノースな
どが挙げられる。アルキリデン基の具体例として
は、イソプロピリデン基、Ｌ−エトキシエチリデ
ン基などが挙げられ、アルアルキリデン基の具体
例としては、ベンジリデン基、Ｐ−メトキシベン
ジリデン基、Ｐ−ジメチルアミノベンジリデン
基、２・４−ジメトキシベンジリデン基などが挙
げられる。なお、保護基としては、上記のアルキ
リデン基またはアルアルキリデン基に限られない
が、ハロゲン化水素酸の存在下で脱離するものが
好ましい。 In the above general formulas [] and [], R represents pentose, pentose phosphate, or hydrogen which may have a protecting group. Specifically, a typical example of a pentose without a protecting group is β-D
-ribofuranose, 2-deoxy-β-D-ribofuranose, 3-deoxy-β-D-ribofuranose, β-D-arabinofuranose, β-D-xylofuranose, and the like. Representative examples of pentose having a protecting group include 2,3-O-alkylidene or aralkylidene-β-D-ribofuranose, 3,5-O-alkylidene or aralkylidene-β-D-xylofuranose, etc. . Specific examples of the alkylidene group include isopropylidene group, L-ethoxyethylidene group, etc. Specific examples of the aralkylidene group include benzylidene group, P-methoxybenzylidene group, P-dimethylaminobenzylidene group, 2.4 -dimethoxybenzylidene group, etc. Note that the protecting group is not limited to the above-mentioned alkylidene group or aralkylidene group, but those that are eliminated in the presence of hydrohalic acid are preferred.
また、ペントースりん酸の代表例としては、上
記の保護基を有することもあるペントースのりん
酸化物、例えばβ−Ｄ−リボフラノース−５−り
ん酸、２−デオキシ−β−Ｄ−リボフラノース−
５−りん酸、β−Ｄ−アラビノフラノース−５−
りん酸またはこれらのアルカリ塩が挙げられる。 Further, as representative examples of pentose phosphate, pentose phosphoric acid which may have the above-mentioned protecting group, such as β-D-ribofuranose-5-phosphate, 2-deoxy-β-D-ribofuranose-
5-phosphoric acid, β-D-arabinofuranose-5-
Examples include phosphoric acid or alkali salts thereof.
なお、一般式〔〕で表わされる本発明の目的
化合物の最も代表的なものとしては、１−（２−
デオキシ−β−Ｄ−リボフラノシル）チミン（チ
ミジン）、１−β−Ｄ−アラビノフラノシルチミ
ン（アラＴ）、１−β−Ｄ−リボフラノシルチミ
ンおよびこれらの５−りん酸体などが挙げられ
る。 The most typical target compound of the present invention represented by the general formula [] is 1-(2-
Examples include deoxy-β-D-ribofuranosyl)thymine (thymidine), 1-β-D-arabinofuranosylthymine (araT), 1-β-D-ribofuranosylthymine, and their 5-phosphate forms. It will be done.
還元反応
本発明における還元反応は、一般式〔〕で表
わされる原料化合物をハロゲン化水素酸の存在
下、電子移動による還元能を有する金属と反応さ
せることによつて進行する。Reduction Reaction The reduction reaction in the present invention proceeds by reacting the raw material compound represented by the general formula [] with a metal capable of reducing through electron transfer in the presence of a hydrohalic acid.
ハロゲン化水素酸
反応に使用するハロゲン化水素酸としては、塩
酸、臭化水素酸またはヨウ化水素酸が好適であ
る。Hydrohalic acid The hydrohalic acid used in the reaction is preferably hydrochloric acid, hydrobromic acid or hydroiodic acid.
ハロゲン化水素酸は水溶液または含水の水混和
性有機溶媒の溶液として使用される。水混和性有
機溶媒としては、ジメチルホルムアミド
（DMF）、ジメチルアセトアミド（DMAC）、ジメ
チルスルホキシド（DMSO）、アセトン、ジオキ
サン、グライム、ジグライム、メタノール、エタ
ノールなどが挙げられる。 The hydrohalic acid is used as an aqueous solution or as a solution in a water-containing water-miscible organic solvent. Examples of water-miscible organic solvents include dimethylformamide (DMF), dimethylacetamide (DMAC), dimethylsulfoxide (DMSO), acetone, dioxane, glyme, diglyme, methanol, ethanol, and the like.
ハロゲン化水素酸の使用量は、原料化合物に対
して５〜200倍当量、好ましくは20〜40倍当量で
ある。 The amount of hydrohalic acid used is 5 to 200 times equivalent, preferably 20 to 40 times equivalent, relative to the raw material compound.
反応溶液中のハロゲン化水素酸の濃度は、通常
約20％以上、特に20〜60％程度が好適である。 The concentration of hydrohalic acid in the reaction solution is usually about 20% or more, preferably about 20 to 60%.
金 属
反応に使用する金属は、反応溶液との接触が良
好な形態であればよい。特に粉末状のものが好ま
しい。Metal The metal used in the reaction may be in a form that allows good contact with the reaction solution. Particularly preferred is powder.
金属の種類としては、本発明方法の条件下で電
子移動による還元能を有するものであればよく、
具体的には亜鉛、スズ、鉄などが挙げられる。特
に亜鉛を使用すれば、反応は効率良く進行する。 The metal may be any metal as long as it has the ability to reduce by electron transfer under the conditions of the method of the present invention.
Specific examples include zinc, tin, and iron. In particular, if zinc is used, the reaction will proceed efficiently.
金属の使用量は、原料化合物に対して５〜50倍
当量、特に５〜20倍当量が好適である。 The amount of metal to be used is preferably 5 to 50 times equivalent, particularly 5 to 20 times equivalent, relative to the raw material compound.
反応条件
本発明の還元反応は、反応温度０〜60℃、好ま
しくは０〜15℃、反応時間0.5〜２時間、好まし
くは0.5〜１時間程度で完了する。Reaction Conditions The reduction reaction of the present invention is completed at a reaction temperature of 0 to 60°C, preferably 0 to 15°C, and a reaction time of 0.5 to 2 hours, preferably about 0.5 to 1 hour.
単離精製
還元反応の完了後、反応液より一般式〔〕で
表わされる目的化合物を単離精製する方法は特に
限定されない。例えば、反応液のPHを調節して金
属のハロゲン化物を水酸化物として沈澱させると
ともに目的化合物も沈澱させ、沈澱物よりシユウ
酸などの試薬やイオン交換樹脂を使用して金属を
除き、さらに必要に応じてイオン交換樹脂、吸着
樹脂、活性炭処理、再結晶法などによつて精製す
ることにより目的化合物を得ることができる。Isolation and Purification After completion of the reduction reaction, the method for isolating and purifying the target compound represented by the general formula [] from the reaction solution is not particularly limited. For example, by adjusting the pH of the reaction solution, metal halides are precipitated as hydroxides, and the target compound is also precipitated, and then metals are removed from the precipitate using a reagent such as oxalic acid or an ion exchange resin. The desired compound can be obtained by purification using an ion exchange resin, adsorption resin, activated carbon treatment, recrystallization method, etc., depending on the purpose.
次に実施例を挙げて本発明をより具体的に説明
する。 Next, the present invention will be described in more detail with reference to Examples.
実施例 １
５−ハイドロキシメチル−2′・3′−Ｏ−イソプ
ロピリデンウリジン〔１−（２・３−Ｏ−イソプ
ロピリデン−β−Ｄ−リボフラノシル）−５−ハ
イドロキシメチルウラシル〕10ｇを52％ヨウ化水
素酸110mlに溶解させ、攪拌下、室温で1.5時間反
応させた。Example 1 10 g of 5-hydroxymethyl-2',3'-O-isopropylidene uridine [1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-hydroxymethyluracil] was added to 52% iodine. It was dissolved in 110 ml of hydrohydric acid and reacted for 1.5 hours at room temperature with stirring.
上記反応液を15℃以下に冷却しながら亜鉛末20
ｇを加えた後、室温で45分間攪拌反応させた。 While cooling the above reaction solution to below 15℃, add 20% zinc powder.
After adding g, the mixture was stirred and reacted at room temperature for 45 minutes.
反応終了後、不溶の亜鉛末を過して除き、
液を10N水酸化ナトリウムでPH8.0に調節した
後、冷却し、生成した沈澱物を取した。沈澱物
を500mlの水に懸濁させ、シユウ酸29ｇを添加
し、生成したシユウ酸亜鉛を過して除き、液
を強酸性カチオン交換樹脂（Ｈ型）250mlカラム
と弱塩基性アニオン交換樹脂（OH型）340mlカ
ラムに通過させ、通過液と洗液を合せて濃縮乾固
した。この残渣を水−エタノール（１：１）によ
つて再結晶し、５−メチルウリジン〔１−β−Ｄ
−リボフラノシルチミン〕の針状晶6.9ｇ（収率
84％）を得た。 After the reaction is complete, remove the undissolved zinc powder by filtration.
After adjusting the pH of the liquid to 8.0 with 10N sodium hydroxide, it was cooled and the formed precipitate was collected. The precipitate was suspended in 500 ml of water, 29 g of oxalic acid was added, the produced zinc oxalate was removed by filtration, and the liquid was separated into a 250 ml column of strongly acidic cation exchange resin (H type) and a weakly basic anion exchange resin ( The mixture was passed through a 340 ml column (OH type), and the passed liquid and washing liquid were combined and concentrated to dryness. This residue was recrystallized from water-ethanol (1:1) to give 5-methyluridine [1-β-D
- 6.9 g of needle-shaped crystals of ribofuranosylthymine (yield
84%).
融点183〜185℃
紫外線吸収スペクトル λ０．１Ｎ−ＨＣｌ ｎａｘ267n
ｍ
λ０．１Ｎ−ＨＣｌ ｎｉｏ235nｍ
元素分析値
Ｃ（％） Ｈ（％） Ｎ（％）
実測値 46.49 5.50 10.83
計算値 46.51 5.46 10.85
（C10H14N2O6として）
実施例 ２
５−ハイドロキシメチル−2′・3′−Ｏ−イソプ
ロピリデンウリジン１ｇを47％臭化水素酸10mlに
溶解させ、攪拌下、室温で1.5時間反応させた。Melting point 183-185℃ Ultraviolet absorption spectrum λ 0 . 1N-HCl nax 267n
m λ 0 . 1N-HCl nio 235nm Elemental analysis value C (%) H (%) N (%) Actual value 46.49 5.50 10.83 Calculated value 46.51 5.46 10.85 (as C 10 H 14 N 2 O 6 ) Example 2 5-hydroxymethyl-2 1 g of '.3'-O-isopropylidene uridine was dissolved in 10 ml of 47% hydrobromic acid, and reacted with stirring at room temperature for 1.5 hours.
上記反応液に亜鉛末２ｇを氷冷下加え、室温で
45分間、攪拌反応させた。 Add 2g of zinc powder to the above reaction solution under ice cooling, and let it cool at room temperature.
The reaction was stirred for 45 minutes.
反応終了後、不溶の亜鉛末を過して除き、
液を実施例１と同様に操作して脱塩した。イオン
交換樹脂カラムより得られた溶液を濃縮乾固し、
残渣を水：エタノール（１：１）から再結晶して
５−メチルウリジン500mg（収率61％）を得た。 After the reaction is complete, remove the undissolved zinc powder by filtration.
The liquid was desalted in the same manner as in Example 1. The solution obtained from the ion exchange resin column was concentrated to dryness,
The residue was recrystallized from water:ethanol (1:1) to obtain 500 mg of 5-methyluridine (yield 61%).
融点183〜185℃
紫外線吸収スペクトル λ０．１Ｎ−ＨＣｌ ｎａｘ267n
ｍ
λ０．１Ｎ−ＨＣｌ ｎｉｏ235nｍ
元素分析値
Ｃ（％） Ｈ（％） Ｎ（％）
実測値 46.38 5.63 10.81
計算値 46.51 5.46 10.85
（C10H14N2O6として）
実施例 ３
５−ハイドロキシメチル−2′・3′−Ｏ−イソプ
ロピリデンウリジン１ｇを35％塩酸に溶解させ攪
拌下、室温で1.5時間反応させた。Melting point 183-185℃ Ultraviolet absorption spectrum λ 0 . 1N-HCl nax 267n
m λ 0 . 1N-HCl nio 235nm Elemental analysis value C (%) H (%) N (%) Actual value 46.38 5.63 10.81 Calculated value 46.51 5.46 10.85 (as C 10 H 14 N 2 O 6 ) Example 3 5-hydroxymethyl-2 1 g of '.3'-O-isopropylidene uridine was dissolved in 35% hydrochloric acid and reacted with stirring at room temperature for 1.5 hours.
上記反応液に亜鉛末２ｇを氷冷下加え、１時
間、攪拌反応させた。 2 g of zinc powder was added to the above reaction solution under ice cooling, and the mixture was reacted with stirring for 1 hour.
以下、実施例１と同様に操作して脱塩し、脱塩
した溶液を濃縮乾固して得られたアメ状残渣をシ
リカゲルクロマトグラフイーによつて分離精製し
て５−メチルウリジン427mg（収率52％）を得
た。 Hereinafter, desalting was performed in the same manner as in Example 1, and the desalted solution was concentrated to dryness. The resulting candy-like residue was separated and purified by silica gel chromatography to obtain 427 mg of 5-methyluridine rate of 52%).
融点183〜185℃
紫外線吸収スペクトル λ０．１Ｎ−ＨＣｌ ｎａｘ267n
ｍ
λ０．１Ｎ−ＨＣｌ ｎｉｏ235nｍ
元素分析値
Ｃ（％） Ｈ（％） Ｎ（％）
実測値 46.39 5.47 10.81
計算値 46.51 5.46 10.85
（C10H14N2O6として）
実施例 ４
５−ハイドロキシメチル−2′−デオキシウリジ
ン〔１−（２−デオキシ−β−Ｄ−リボフラノシ
ル）−５−ハイドロキシメチルウラシル〕１ｇを
氷冷した52％ヨウ化水素酸10mlに溶解させ、攪拌
下、1.5時間反応させた。Melting point 183-185℃ Ultraviolet absorption spectrum λ 0 . 1N-HCl nax 267n
m λ 0 . 1N-HCl nio 235nm Elemental analysis value C (%) H (%) N (%) Actual value 46.39 5.47 10.81 Calculated value 46.51 5.46 10.85 (as C 10 H 14 N 2 O 6 ) Example 4 5-hydroxymethyl-2 1 g of '-deoxyuridine [1-(2-deoxy-β-D-ribofuranosyl)-5-hydroxymethyluracil] was dissolved in 10 ml of ice-cooled 52% hydroiodic acid, and reacted with stirring for 1.5 hours.
上記の反応液に亜鉛末２ｇを加え、氷冷下、１
時間、攪拌反応させた。 Add 2 g of zinc powder to the above reaction solution, and add 1 g of zinc powder under ice cooling.
The reaction was stirred for an hour.
反応終了後、反応液を過し、液を10N水酸
化ナトリウムでPH８に調節し、生成した沈澱物を
取し、これを水100mlに懸濁した後、ギ酸を滴
下して溶解させ、強酸性カチオン交換樹脂（Ｈ
型）60mlカラムと弱塩基性アニオン交換樹脂
（OH型）80mlカラムを通過させた後、通過液と
水洗液を合せて濃縮乾固した。残渣を水から再結
晶してチミジン〔１−（２−デオキシ−β−Ｄ−
リボフラノシル）チミン〕の針状晶430mg（収率
45.8％）を得た。 After the reaction is complete, filter the reaction solution, adjust the pH of the solution to 8 with 10N sodium hydroxide, collect the formed precipitate, suspend it in 100ml of water, add dropwise formic acid to dissolve it, and add strong acid. Cation exchange resin (H
After passing through a 60 ml column (type) and an 80 ml column of weakly basic anion exchange resin (OH type), the passed liquid and the water washing liquid were combined and concentrated to dryness. The residue was recrystallized from water to give thymidine [1-(2-deoxy-β-D-
430 mg of needle-like crystals of ribofuranosyl)thymine (yield
45.8%).
融点183〜185℃
紫外線吸収スペクトル λ０．１Ｎ−ＨＣｌ ｎａｘ267n
ｍ
λ０．１Ｎ−ＨＣｌ ｎｉｏ235nｍ
元素分析値
Ｃ（％） Ｈ（％） Ｎ（％）
実測値 49.48 5.97 11.53
計算値 49.59 5.83 11.56
（C10H14N2O5として）
実施例 ５
５−ハイドロキシメチル１−β−Ｄ−アラビノ
フラノシルウラシル１ｇを52％ヨウ化水素酸10ml
に溶解し、攪拌下、室温で1.5時間反応させた。Melting point 183-185℃ Ultraviolet absorption spectrum λ 0 . 1N-HCl nax 267n
m λ 0 . 1N-HCl nio 235nm Elemental analysis value C (%) H (%) N (%) Actual value 49.48 5.97 11.53 Calculated value 49.59 5.83 11.56 (as C 10 H 14 N 2 O 5 ) Example 5 5-Hydroxymethyl 1- 1g of β-D-arabinofuranosyluracil in 10ml of 52% hydroiodic acid
and reacted for 1.5 hours at room temperature under stirring.
上記の反応液に亜鉛末２ｇを加え、氷冷下、１
時間、攪拌反応させた。 Add 2 g of zinc powder to the above reaction solution, and add 1 g of zinc powder under ice cooling.
The reaction was stirred for an hour.
反応終了後、反応液を過し、液を10N水酸
化ナトリウムでPH８に調節して冷却した。生成し
た沈澱を取後、水100mlに懸濁し、6N塩酸を滴
下して溶解させ、強酸性カチオン交換樹脂（Ｈ
型）60mlカラムを通過させた。通過液と水洗液を
合せ、水酸化ナトリウムで中和後、濃縮して析出
した結晶を取し、水から再結晶して５−メチル
−１−β−Ｄ−アラビノフラノシルウラシル〔１
−β−Ｄ−アラビノフラノシルチミン〕の針状晶
620mg（収率65.8％）を得た。 After the reaction was completed, the reaction solution was filtered, the pH of the solution was adjusted to 8 with 10N sodium hydroxide, and the solution was cooled. After removing the formed precipitate, suspend it in 100 ml of water, add 6N hydrochloric acid dropwise to dissolve it, and add strongly acidic cation exchange resin (H
type) was passed through a 60ml column. The filtered liquid and the water washing liquid were combined, neutralized with sodium hydroxide, concentrated, precipitated crystals were collected, and recrystallized from water to obtain 5-methyl-1-β-D-arabinofuranosyluracil [1
-β-D-arabinofuranosylthymine] needle crystals
620 mg (yield 65.8%) was obtained.
融点238〜242℃
紫外線吸収スペクトル λ０．１Ｎ−ＨＣｌ ｎａｘ268n
ｍ
λ０．１Ｎ−ＨＣｌ ｎｉｏ236nｍ
元素分析値
Ｃ（％） Ｈ（％） Ｎ（％）
実測値 46.39 5.57 10.72
計算値 46.51 5.46 10.85
（C10H14N2O6として）
実施例 ６
５−ハイドロキシ−2′・3′−Ｏ−イソプロピリ
デンウリジン500mgを52％ヨウ化水素酸５mlに溶
解した後、スズ末２ｇを加え、２時間攪拌反応さ
せた。Melting point 238-242℃ Ultraviolet absorption spectrum λ 0 . 1N-HCl nax 268n
m λ 0 . 1N-HCl nio 236nm Elemental analysis value C (%) H (%) N (%) Actual value 46.39 5.57 10.72 Calculated value 46.51 5.46 10.85 (as C 10 H 14 N 2 O 6 ) Example 6 5-hydroxy-2' - After dissolving 500 mg of 3'-O-isopropylidene uridine in 5 ml of 52% hydroiodic acid, 2 g of tin powder was added and the reaction was stirred for 2 hours.
反応後、生成した沈澱物を過して除き、液
を中和後、濃縮した。得られた濃縮液をペーパー
クロマトグラフイー（展開溶媒 イソ酪酸：濃ア
ンモニア：水＝66：１：33）で分析した結果、５
−メチルウリジン（収率25.6％）が合成されてい
た。 After the reaction, the generated precipitate was removed by filtration, the liquid was neutralized, and then concentrated. As a result of analyzing the obtained concentrate by paper chromatography (developing solvent: isobutyric acid: concentrated ammonia: water = 66:1:33), 5
-Methyluridine (yield 25.6%) was synthesized.
Claims (1)
ス、ペントースりん酸または水素を示す。〕で表
わされる５−ハイドロキシメチルピリミジン誘導
体をハロゲン化水素酸存在下、電子移動による還
元能を有する金属と反応せしめ、５位ハイドロキ
シメチル基をメチル基に還元して一般式〔〕 〔式中、Ｒは前記と同意義である。〕で表わされる
５−メチルピリミジン誘導体を得ることを特徴と
する５−メチルピリミジン誘導体の製造法。 ２ 一般式〔〕で表わされる５−ハイドロキシ
メチルピリミジン誘導体において、Ｒがβ−Ｄ−
リボフラノース、２・３−Ｏ−アルキリデン−β
−Ｄ−リボフラノース、２・３−Ｏ−アルアルキ
リデン−β−Ｄ−リボフラノース、２−デオキシ
−β−Ｄ−リボフラノース、３−デオキシ−β−
Ｄ−リボフラノース、β−Ｄ−アラビノフラノー
ス、β−Ｄ−キシロフラノース、３・５−Ｏ−ア
ルキリデン−β−Ｄ−キシロフラノース、３・５
−Ｏ−アルアルキリデン−β−Ｄ−キシロフラノ
ース、β−Ｄ−リボフラノース−５−りん酸もし
くはそのアルカリ塩、２−デオキシ−β−Ｄ−リ
ボフラノース−５−りん酸もしくはそのアルカリ
塩、β−Ｄ−アラビノフラノース−５−りん酸も
しくはそのアルカリ塩、または水素である特許請
求の範囲第１項記載の５−メチルピリミジン誘導
体の製造法。 ３ 一般式〔〕で表わされる５−メチルピリミ
ジン誘導体において、Ｒがβ−Ｄ−リボフラノー
ス、２−デオキシ−β−Ｄ−リボフラノース、３
−デオキシ−β−Ｄ−リボフラノース、β−Ｄ−
アラビノフラノース、β−Ｄ−キシロフラノー
ス、β−Ｄ−リボフラノース−５−りん酸もしく
はそのアルカリ塩、２−デオキシ−β−Ｄ−リボ
フラノース−５−りん酸もしくはそのアルカリ
塩、β−Ｄ−アラビノフラノース−５−りん酸も
しくはそのアルカリ塩、または水素である特許請
求の範囲第１項記載の５−メチルピリミジン誘導
体の製造法。 ４ ハロゲン化水素酸が塩酸、臭化水素酸または
ヨウ化水素酸である特許請求の範囲第１項〜第３
項いずれかに記載の５−メチルピリミジン誘導体
の製造法。 ５ 電子移動による還元能を有する金属が亜鉛、
スズまたは鉄である特許請求の範囲第１項〜第４
項いずれかに記載の５−メチルピリミジン誘導体
の製造法。[Claims] 1. General formula [] [In the formula, R represents a pentose, pentose phosphate, or hydrogen which may have a protecting group. ] A 5-hydroxymethylpyrimidine derivative represented by the formula [] is reacted with a metal having a reducing ability through electron transfer in the presence of a hydrohalic acid, and the hydroxymethyl group at the 5-position is reduced to a methyl group. [In the formula, R has the same meaning as above. A method for producing a 5-methylpyrimidine derivative, which comprises obtaining a 5-methylpyrimidine derivative represented by the following. 2 In the 5-hydroxymethylpyrimidine derivative represented by the general formula [], R is β-D-
Ribofuranose, 2,3-O-alkylidene-β
-D-ribofuranose, 2,3-O-alalkylidene-β-D-ribofuranose, 2-deoxy-β-D-ribofuranose, 3-deoxy-β-
D-ribofuranose, β-D-arabinofuranose, β-D-xylofuranose, 3,5-O-alkylidene-β-D-xylofuranose, 3,5
-O-Aralkylidene-β-D-xylofuranose, β-D-ribofuranose-5-phosphate or its alkali salt, 2-deoxy-β-D-ribofuranose-5-phosphate or its alkali salt, β -D-arabinofuranose-5-phosphoric acid or an alkali salt thereof, or hydrogen, the method for producing a 5-methylpyrimidine derivative according to claim 1. 3 In the 5-methylpyrimidine derivative represented by the general formula [], R is β-D-ribofuranose, 2-deoxy-β-D-ribofuranose, 3
-deoxy-β-D-ribofuranose, β-D-
Arabinofuranose, β-D-xylofuranose, β-D-ribofuranose-5-phosphate or its alkali salt, 2-deoxy-β-D-ribofuranose-5-phosphate or its alkali salt, β-D -arabinofuranose-5-phosphoric acid or its alkali salt, or hydrogen, the method for producing a 5-methylpyrimidine derivative according to claim 1. 4 Claims 1 to 3 in which the hydrohalic acid is hydrochloric acid, hydrobromic acid, or hydroiodic acid
2. A method for producing a 5-methylpyrimidine derivative according to any one of the above. 5. Zinc is a metal that has the ability to reduce through electron transfer.
Claims 1 to 4 which are tin or iron
2. A method for producing a 5-methylpyrimidine derivative according to any one of the above.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7913679A JPS565466A (en) | 1979-06-25 | 1979-06-25 | Preparation of 5-methylpyrimidine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7913679A JPS565466A (en) | 1979-06-25 | 1979-06-25 | Preparation of 5-methylpyrimidine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS565466A JPS565466A (en) | 1981-01-20 |
| JPS6152828B2 true JPS6152828B2 (en) | 1986-11-14 |
Family
ID=13681530
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7913679A Granted JPS565466A (en) | 1979-06-25 | 1979-06-25 | Preparation of 5-methylpyrimidine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS565466A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4694061A (en) * | 1983-10-12 | 1987-09-15 | Ciba-Geigy Corporation | Radiation-sensitive polycondensates, processes for their preparation coated material and its use |
-
1979
- 1979-06-25 JP JP7913679A patent/JPS565466A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS565466A (en) | 1981-01-20 |
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