JPS63159371A - 6,7-dihydroxyisoquinoline, its hydrohalide and production thereof - Google Patents
6,7-dihydroxyisoquinoline, its hydrohalide and production thereofInfo
- Publication number
- JPS63159371A JPS63159371A JP61305511A JP30551186A JPS63159371A JP S63159371 A JPS63159371 A JP S63159371A JP 61305511 A JP61305511 A JP 61305511A JP 30551186 A JP30551186 A JP 30551186A JP S63159371 A JPS63159371 A JP S63159371A
- Authority
- JP
- Japan
- Prior art keywords
- dihydroxyisoquinoline
- hydrohalide
- group
- salt
- protected
- 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
- LOIDKAGDLUKYNE-UHFFFAOYSA-N isoquinoline-6,7-diol Chemical compound C1=NC=C2C=C(O)C(O)=CC2=C1 LOIDKAGDLUKYNE-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- YCIMNLLNPGFGHC-UHFFFAOYSA-N o-dihydroxy-benzene Natural products OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- 239000007900 aqueous suspension Substances 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 6
- 239000002253 acid Substances 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 abstract description 6
- 125000006239 protecting group Chemical group 0.000 abstract description 4
- 241000894006 Bacteria Species 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 235000011121 sodium hydroxide Nutrition 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 2
- 239000000126 substance Substances 0.000 abstract 2
- 229930186147 Cephalosporin Natural products 0.000 abstract 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 abstract 1
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 229940124587 cephalosporin Drugs 0.000 abstract 1
- 125000001271 cephalosporin group Chemical class 0.000 abstract 1
- 239000000470 constituent Substances 0.000 abstract 1
- 238000001228 spectrum Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- -1 bapaverine Natural products 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical class C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- QJTBIAMBPGGIGI-UHFFFAOYSA-N Papaveraldine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)C1=NC=CC2=CC(OC)=C(OC)C=C12 QJTBIAMBPGGIGI-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical group FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- JJZIJKXUHDFVGX-UHFFFAOYSA-N (6,7-dimethoxyisoquinolin-1-yl)-(3,4-dimethoxyphenyl)methanol Chemical compound C1=C(OC)C(OC)=CC=C1C(O)C1=NC=CC2=CC(OC)=C(OC)C=C12 JJZIJKXUHDFVGX-UHFFFAOYSA-N 0.000 description 1
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 1
- QFNFXYPFSYJCDF-UHFFFAOYSA-N 1-hydroxy-2h-isoquinolin-3-one Chemical compound C1=CC=CC2=C(O)NC(=O)C=C21 QFNFXYPFSYJCDF-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LUMNWCHHXDUKFI-UHFFFAOYSA-N 5-bicyclo[2.2.1]hept-2-enylmethanol Chemical group C1C2C(CO)CC1C=C2 LUMNWCHHXDUKFI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241000069157 Miconia aeruginosa Species 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 240000000249 Morus alba Species 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Other In-Based Heterocyclic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の技術分野〉
本発明は新規な化合物である6、7−ジムイド1]キシ
イソキノリン或いはそのハロゲン化水f[塩、およびそ
れらの%ih法に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Technical Field> The present invention relates to a novel compound, 6,7-diimide 1]xisoquinoline, or its halogenated water f[salt], and a %ih method thereof.
更に訂#111には、緑寝菌J3よびグラム陰性菌tこ
対する非常に11″hい活f)1を有するセファ[」ス
ポリン誘導体の3位側鎖となり得る、6,7−ジムイド
1]キシイソキノリンのハロゲン化水素M塩、 、7−
ジハイドL1キシイソキノリンJ3J、びそれらの’N
yp=法に関する。Furthermore, in revision #111, a 6,7-diimoid 1, which can be the 3-position side chain of a sporin derivative, has a very 11"h activity f)1 against M. aeruginosa J3 and Gram-negative bacteria. Hydrogen halide M salt of xyisoquinoline, , 7-
Dihyde L1 xyisoquinoline J3J, and their 'N
Regarding the yp = law.
〈従来技術〉
イソキノリン骨格の6,7−位にメ)〜キシ基を樽入し
た6、7−シメトキシイソキノリンは鎮が桑である阿片
アルカロイドのバパベリン、パパベリノールおよびパパ
ベラルジン等の合成出発原料として種々の合成法か知ら
れている[例えばJOIIrnalor the Am
QrlCFlfl ChOIIIICal 5OCIC
!(V 794.3773貞(19!17)参照]。<Prior art> 6,7-Simethoxyisoquinoline, which has methoxy groups at the 6,7-positions of the isoquinoline skeleton, is used as a starting material for the synthesis of opium alkaloids such as bapaverine, papaverinol, and papaveraldine, which are derived from mulberry. Synthesis methods are known [e.g. JOII RNA the Am
QrlCFfl ChOIIICal 5OCIC
! (See V 794.3773 Sada (19!17)).
しかしながら、、7−ジハイトL1キシイソキノリン自
体J3よびそのハ[1グン化水素酸塩は知られていなか
った。However, 7-dihyte L1 xyisoquinoline itself J3 and its ha[1hydrogonide] were not known.
〈発明の目的〉
本発明の目的は新規なイソキノリン誘導体である6、7
−ジハイトし」キシイソキノリンの八L」グン化水素酸
塩および、7−ジハイドロキシイソキノリンを提供する
こと(こある。史に訂しくは広い抗菌スペクI〜ルを有
する、特にBc菌およびグラム陰性菌に対し非常に!1
1い活↑(1を石するヒノアL1スitzリン誘脣休の
3位側鎖の構成+A利となり得る6゜7−シハイ1〜L
1キシイソキノリンまたはそのハ(:(ゲン化水素酸塩
を(;?供することにある。<Object of the invention> The object of the present invention is a novel isoquinoline derivative6,7
- To provide an 8-L-hydrogunide salt of ``dihydroxyisoquinoline'' and 7-dihydroxyisoquinoline. Very effective against bacteria!1
1 active ↑ (Hinoa L1 switching 1, 3-position side chain configuration of phosphorus induction rest + 6゜7-Shihi 1~L that can be A advantage)
The purpose is to provide 1-xisoquinoline or its (:(hydrogenide).
本発明の仙の[]的は6,7−ジハイト[1キシイソキ
ノリンハ[]グン化水索酸−のI!Aha法を提供する
ことにある。The target of the present invention is the I! It is to provide the Aha method.
水5と明の史に他のl」的は6,7−ジハイト[]1キ
シイソキノリンの製造法を提供することにある。Another objective of Shui 5 and Ming's history is to provide a method for producing 6,7-dihyto[]1xisoquinoline.
本発明の他の目的J3よび利点は以下の記)Lから一層
明らかとなるであろう。Other objects and advantages of the present invention will become more apparent from the following paragraph L.
本発明によれば、これらの目的J3よび利点は力jコー
ル保護基によって保護された6、7−ジハイド(」キシ
イソキノリンを、ハ]」グン化水素酸によって)脱保護
することによる6、7−ジハイドロキシイソキノリンの
ハロゲン化水素酸塩の製3Vi法および6,7−ジハイ
ドロキシイソキノリンのハ1」グン化水素酸塩の水溶液
または水懸濁液を凹4,5〜PH10、0に調製するこ
とによる6、7−ジハイドロキシイソキノリンの%J
)kj法によって達成される。According to the present invention, these objects and advantages are obtained by deprotecting 6,7-dihydrides (xyisoquinolines, by hydrogonic acid) protected by 6,7-col protecting groups. - Preparation of hydrohalide salt of dihydroxyisoquinoline 3Vi method and preparation of aqueous solution or aqueous suspension of hydrogunide salt of 6,7-dihydroxyisoquinoline to a pH of 4,5 to 10,0 Possibly %J of 6,7-dihydroxyisoquinoline
)kj method.
本発明にお1ノる6、7−ジハイドロキシイソキノリン
のハロゲン化水素酸塩としては塩酸塩、臭化水素酸塩お
よびヨウ化水素V塩があげられる。Examples of the hydrohalide salt of 6,7-dihydroxyisoquinoline in the present invention include hydrochloride, hydrobromide and hydrogen iodide V salt.
また本発明の6,7−ジハイドロキシイソキノリンおよ
びそのハロゲン化水素酸塩は結晶中に結晶水として水を
含有することができる。Further, the 6,7-dihydroxyisoquinoline and its hydrohalide salt of the present invention can contain water as crystal water in the crystal.
次に本発明について更に詳細に説明する。Next, the present invention will be explained in more detail.
本発明における6、7−ジハイドロキシイソキノリンの
ハロゲン化水素酸塩は、カテコール保護基によって保護
されたら、7−ジムイト1]キシイソキノリンをハロゲ
ン化水ff1Mの存在下加熱しで1税保護することにJ
:って1qることができる。The hydrohalide salt of 6,7-dihydroxyisoquinoline in the present invention, once protected by a catechol protecting group, can be protected by heating 7-dimite 1]xyisoquinoline in the presence of 1M of halogenated water. J
: You can do 1q.
本発明の“前記カテコール保護基によって保護された6
、7−ジハイドロキシイソキノリン″にお()るカテコ
ール保1pとしては、−11Qにカテコールの保護に使
用される保護基であればよく、殊に1受述する脱保護に
よって、1悦離し易いものが好ましい。通常2価の低級
アルキル塁、低級シクロアルキル基或いは置換されたこ
れらの塁であるしのが保護基として有利に使用される。According to the present invention, “6 protected by said catechol protecting group”
, 7-dihydroxyisoquinoline'' may be any protective group used for protecting catechol at -11Q, especially one that can be easily removed by the deprotection described in 1. Usually, a divalent lower alkyl group, a lower cycloalkyl group, or a substituted group thereof is advantageously used as a protecting group.
かかるカデニ1−ル保護基の具体例としては2価のメチ
ル基、イソプロピル塁、デトラヒトL]ピラニル基、シ
フ[」プ[lピルメチル基、シクロヘキシル塁、ペンシ
ル基、4−ピコリル基等があげられる。またメブレン基
、ジメチルメヂレン基、シクロl\キシリゾ′ン塁、ジ
フェニルメチレン基等もあげられる。6fましくは2個
のメチル基で保護されたジメトキシ体またはメチレン基
で保護されたメブレンシ;114〜シ休かあげられる。Specific examples of such cadenyl-protecting groups include divalent methyl group, isopropyl group, detrachtyl L]pyranyl group, Schif['p[l-pylmethyl group, cyclohexyl group, pencil group, 4-picolyl group, etc. . Also included are meblene group, dimethylmethylene group, cyclol\xylizone group, diphenylmethylene group, and the like. Preferably, a dimethoxy compound protected with two methyl groups or a dimethoxy compound protected with a methylene group;
本発明の反応に使用されるハロゲン化水素酸としては、
澗塩酸、臭化水素酸またはヨウ化水索酸か挙げられる。As the hydrohalic acid used in the reaction of the present invention,
Examples include hydrochloric acid, hydrobromic acid or iodohydrochloric acid.
ハロゲン化水素酸の吊は用いる1京料イソキノリン誘う
9体にり(1して2倍−しル以上、好ましくは3倍−し
ル以上用いる。加熱湿度は好ましくは100 ’C以上
200°C以下で、必要なら封管、 7J−1−クレー
プ等で加住干反応覆ることもてきる。The amount of hydrohalic acid to be used is 1 to 2 times the amount of isoquinoline to be used, preferably 3 times or more. The heating humidity is preferably 100'C to 200°C. In the following, if necessary, you can cover the reaction with a sealed tube, 7J-1-crepe, etc.
この際特に沸点で加熱上生成する低沸分を除去しつつ反
応することにより好ましい結果がelられる。At this time, preferable results can be obtained by performing the reaction while removing low-boiling components generated during heating at the boiling point.
反応11・1間は30分から20時間稈葭て好ましくは
114間から1011;−)間である。The reaction time is preferably between 114 and 1011;-) for 30 minutes to 20 hours.
生成したハロゲン化水素酸塩は艮応渥合液を冷却し)戸
別するか或い4.1ltfa縮または乾固し必要ならハ
ロゲン化水素V等で際結晶することにより+’i”:j
紳磨で得られる。The generated hydrohalide salt is purified by cooling the combined liquid, separating the mixture, condensing it to 4.1 ltfa or drying it, and if necessary crystallizing it with hydrogen halide V, etc.
Obtained with Shinma.
また該ハロゲン化水素酸塩は三弗化ホウ素エーテル11
1体、塩化アルミニウム、または臭化アルミニウムとエ
チルメルカブタン中で反応2¥Uることによって−b得
られろ。Further, the hydrohalide salt is boron trifluoride ether 11
1, -b can be obtained by reaction with aluminum chloride or aluminum bromide in ethyl mercabutane.
次に6,7−ジハイドロキシイソキノリンの41口法に
ついてム■)圭する。Next, we will discuss the 41-unit method for 6,7-dihydroxyisoquinoline.
、7−ジハイト1」キシイソキノリンは、7−シハイト
[」キシイソキノリンのハロゲン化水素酸塩を水中に溶
解または懸濁しこれにアルカリを加えるごとにより1q
ることができる。, 7-dihyto['xyisoquinoline] is produced by dissolving or suspending the hydrohalide of 7-dihyto['xyisoquinoline] in water and adding an alkali to it to produce 1q.
can be done.
この際、水中に水に溶解する有機溶媒例えばアセトン、
メタノール、エタノール、NN−ジメチルホルムアミト
、ジメヂルスルフAキシド、テ1〜ラヒドロフランまた
はジオキリン等を含有さlてb良い。At this time, an organic solvent that dissolves in water, such as acetone,
It may contain methanol, ethanol, NN-dimethylformamide, dimethyl sulfur oxide, tetrahydrofuran, diochirin, or the like.
使用するアルカリとしてはアルカリ金属の水酸化物或い
はぞの塩を用いるのか好ましく、例えば苛性ソーダ、?
信[4カリ、炭酸ソーダ、小炭酸ソーダ或いはそれらの
水溶液があげられる。The alkali used is preferably an alkali metal hydroxide or its salt, such as caustic soda, etc.
[4] Potassium, soda carbonate, small soda soda, or aqueous solutions thereof.
この際、溶液の[〉11を4.5〜10.好ましくは4
.7へ・9、更に好ましくは4.8〜6,5に調整する
。pH4,5未満では、7−ジハイトロキシイソキノリ
ンは生成し難く、一方pHIOを越えると、塩を作って
溶解する。この反応温石は0°C〜80°C,好ましく
は5℃〜40°Cの範囲か右利である。At this time, the [>11] of the solution was 4.5 to 10. Preferably 4
.. Adjust to 7.9, more preferably 4.8 to 6.5. Below pH 4.5, 7-dihydroxyisoquinoline is difficult to produce, while above pHIO, salt is formed and dissolved. This reaction hot stone has a temperature range of 0°C to 80°C, preferably 5°C to 40°C.
、7−シハイドロキシイソ4−ノリンはこうしくpl+
を調整することにより得られた結晶を)戸別し必要なら
再結晶」ることによって15tられる。, 7-cyhydroxyiso4-noline is thus pl+
The crystals obtained by adjusting the
以下に実施例によって本発明を史に詳細に説明する。The present invention will be explained in detail below by way of examples.
実施例′1
、7−シメトキシイソキノリン18.9gをヨウ化水素
酸く57%) 200 d中、低沸部分を除さながら2
時間沸点で反応した。冷却後)戸別し水洗、アセトン洗
して、7−ジじドロキシイソキノリンヨウ化水素酸塩2
8.0(Jを得た。このものの分析値は下記の通りであ
った。Example '1: 18.9 g of 7-simethoxyisoquinoline was dissolved in hydrogen iodide (57%) at 200 d, while removing the low-boiling portion.
Reacted at boiling point for hours. After cooling) Wash separately with water and acetone to obtain 7-dididroxyisoquinoline hydroiodide 2
8.0 (J) was obtained. The analytical values of this product were as follows.
欧貞;260〜270’C
NMR:(δ: ppm)
7.47(Ift、S)、 7.68(Ill、S)
、 8.24(2tLdd)9.46(ltl、s)
実施例2
上記6,7−ジヒド1」キシイソキノリンヨウ止水IM
塩2.89gを10mjの水に懸濁し、1N−苛1ノl
ソーダ水溶液を加えpH5,0に調整した。260-270'C NMR: (δ: ppm) 7.47 (Ift, S), 7.68 (Ill, S)
, 8.24 (2tLdd) 9.46 (ltl, s) Example 2 The above-mentioned 6,7-dihyde 1''xyisoquinoline iodine water-stop IM
Suspend 2.89 g of salt in 10 mj of water, add 1 mol of 1N caustic acid
Aqueous soda solution was added to adjust the pH to 5.0.
析出する沈澱を)戸別水洗乾燥して14+11の6,7
−シハイドロギシイソキノリンをg7た。Wash and dry the precipitate (14 + 11 6, 7)
-G7 g of dihydroisoquinoline.
故意;274〜278°C
Mass(m/e) 161.0482NMR:(δ
: ppm)
7.06(III、s)、 7.16(ltl、s)、
7.77(211,d+I)8、85(III、 S
)
実施例3
、7 −メJレンジΔニドジイソキノリン17.3(l
を13.7−シメトキシイソキノリン18.99のかわ
りに用いる他は実施例′1と同様にして、7−ジヒド〔
11−ジイソキノリンヨウ化水素M塩27.8!Jを得
た。Intentional; 274-278°C Mass (m/e) 161.0482NMR: (δ
: ppm) 7.06 (III, s), 7.16 (ltl, s),
7.77 (211, d+I) 8, 85 (III, S
) Example 3, 7-MeJ Range Δ Nidodiisoquinoline 17.3(l
7-dihyde [
11-diisoquinoline hydrogen iodide M salt 27.8! I got J.
実施例4
、7−ラメ1〜キシイソキノリン18.9(Jを臭化水
m 1lv2(47% ) 3007!中、低沸部分を
除きなカラ10115間%71点で反応し、冷7JI
i変)戸別して水洗、アレ1−ン洗し6,7 −シヒト
【」キシ臭化水素酸塩20.71をq2p 7こ 。Example 4, 7-lame 1 to xyisoquinoline 18.9 (J to bromide water m 1lv2 (47%) 3007! React at 10115% 71 point, excluding the medium and low boiling parts, cold 7JI
(change) Wash each house with water, wash with water, and add 20.71 q2p of 6,7-cyhydrobromide.
実施例5
、7−シメトキシーイソキノリン189mgを封鎖・注
170°Cで5時間濃塩酸2ml1と艮応し冷7JI後
)戸別し水洗乾燥して6,7−ジヒドロキシ塩酸塩82
mgを151!た。Example 5 189 mg of 7-simethoxyisoquinoline was blocked and reacted with 2 ml of concentrated hydrochloric acid at 170°C for 5 hours.
151 mg! Ta.
Claims (1)
ゲン化水素酸塩。 2、カテコール保護基によって保護された6,7−ジハ
イドロキシイソキノリンを、ハロゲン化水素酸塩の存在
下脱保護せしめることを特徴とする6,7−ジハイドロ
キシイソキノリンのハロゲン化水素酸塩の製造法。 3、6,7−ジハイドロキシイソキノリンのハロゲン化
水素酸塩の水溶液又は水懸濁液を、PH4.5〜PH1
0.0に調製せしめることを特徴とする6、7−ジハイ
ドロキシイソキノリンの製造法。[Claims] 1,6,7-dihydroxyisoquinoline or its hydrohalide salt. 2. A method for producing a hydrohalide salt of 6,7-dihydroxyisoquinoline, which comprises deprotecting 6,7-dihydroxyisoquinoline protected by a catechol protecting group in the presence of a hydrohalide salt. . An aqueous solution or aqueous suspension of a hydrohalide salt of 3,6,7-dihydroxyisoquinoline is prepared at a pH of 4.5 to 1.
A method for producing 6,7-dihydroxyisoquinoline, which comprises preparing 6,7-dihydroxyisoquinoline to a concentration of 0.0.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP61305511A JPS63159371A (en) | 1986-12-23 | 1986-12-23 | 6,7-dihydroxyisoquinoline, its hydrohalide and production thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP61305511A JPS63159371A (en) | 1986-12-23 | 1986-12-23 | 6,7-dihydroxyisoquinoline, its hydrohalide and production thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS63159371A true JPS63159371A (en) | 1988-07-02 |
Family
ID=17946035
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP61305511A Pending JPS63159371A (en) | 1986-12-23 | 1986-12-23 | 6,7-dihydroxyisoquinoline, its hydrohalide and production thereof |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS63159371A (en) |
-
1986
- 1986-12-23 JP JP61305511A patent/JPS63159371A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TW412537B (en) | Cephalosporin derivatives | |
ES2836118T3 (en) | Procedure for the Preparation of a Nitric Oxide Donor Prostaglandin Analog | |
CN105131017A (en) | Preparation method for cefcapene pivoxil hydrochloride | |
JPS59130888A (en) | Crystalline cephem-acid addition salt and manufacture | |
JPS63159371A (en) | 6,7-dihydroxyisoquinoline, its hydrohalide and production thereof | |
JPS5824569A (en) | Purification of imidazole derivative | |
NO135983B (en) | ||
McCasland et al. | 4, 5-dihalo and 3-amino analogs of pyridoxine. New route to 4-deoxypyridoxine | |
Kaye | 2-Lepidyl substituted diamines | |
JPH03176473A (en) | Pyridine-n-oxide derivative and its preparation | |
US2654759A (en) | Derivatives of n-hydroxymethyl | |
CN107513093A (en) | The preparation method of epristeride intermediate and preparation method thereof, epristeride | |
JPS6037109B2 (en) | 5,6,7,3',4',5'-hexahydroxyflavone | |
JPS6016931B2 (en) | Method for producing substituted benzoic acid amide | |
US2558068A (en) | Process of producing j | |
ES8604220A1 (en) | Pyrimidoisoquinoline derivatives. | |
Cromwell et al. | Synthesis and Reactions of α-Acetoxy and α-Benzoxy-β-amino Ketones | |
US2516251A (en) | Penilloic acid and preparation thereof | |
JPS6039264B2 (en) | Method for producing 3-amino-2-hydroxy-4-p-hydroxyphenylbutanoylleucine and its derivatives | |
JPS63211280A (en) | Production of 2-(4-thiazolyl)benzimidazole | |
KR940014415A (en) | 2-thienylimidazo [2,1-b] benzothiazole-3-acetic acid derivatives, their preparation and use in the treatment thereof | |
KR790001070B1 (en) | Process for preparing cephalosporin | |
Postovskii et al. | Investigations in the benzodiazine series: XI. Covalent hydration in a number of tetrazolo [1, 5c] quinazoline derivatives | |
Plašek et al. | Unusual demethylation of 1-dimethylamine-1-carba-closo-dodecarbonate (11) | |
JPS58144377A (en) | Preparation of 5-mercaptotetrazolyl-1-acetic acid |