DK143159B - Fremgangsmaade til fremstilling af 4-hydroxymethyl-1-keto-1,2-dihydrophthalazin eller syreadditionssalte deraf - Google Patents
Fremgangsmaade til fremstilling af 4-hydroxymethyl-1-keto-1,2-dihydrophthalazin eller syreadditionssalte deraf Download PDFInfo
- Publication number
- DK143159B DK143159B DK377872AA DK377872A DK143159B DK 143159 B DK143159 B DK 143159B DK 377872A A DK377872A A DK 377872AA DK 377872 A DK377872 A DK 377872A DK 143159 B DK143159 B DK 143159B
- Authority
- DK
- Denmark
- Prior art keywords
- keto
- dihydrophthalazine
- formula
- hydroxymethyl
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 8
- SPVIEWHOXUYOPN-UHFFFAOYSA-N 4-(hydroxymethyl)-2h-phthalazin-1-one Chemical compound C1=CC=C2C(CO)=NNC(=O)C2=C1 SPVIEWHOXUYOPN-UHFFFAOYSA-N 0.000 title description 5
- 150000003839 salts Chemical class 0.000 title description 4
- 239000002253 acid Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- -1 lithium aluminum hydride Chemical compound 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 150000001340 alkali metals Chemical class 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000004526 pharmaceutical effect Effects 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- YHNOBCUFJJRVOP-UHFFFAOYSA-N 4-oxo-3h-phthalazine-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NNC(=O)C2=C1 YHNOBCUFJJRVOP-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- VSYNNZHXKFVHJY-UHFFFAOYSA-N ethyl 4-oxo-3h-phthalazine-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)=NNC(=O)C2=C1 VSYNNZHXKFVHJY-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QDAWXRKTSATEOP-UHFFFAOYSA-N 2-acetylbenzoic acid Chemical compound CC(=O)C1=CC=CC=C1C(O)=O QDAWXRKTSATEOP-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 101100020289 Xenopus laevis koza gene Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910001507 metal halide Inorganic materials 0.000 description 1
- 150000005309 metal halides Chemical class 0.000 description 1
- MKUYKCWVZJBMOA-UHFFFAOYSA-N methyl 4-oxo-3h-phthalazine-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=NNC(=O)C2=C1 MKUYKCWVZJBMOA-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- JPRPQMBRFZKJDW-UHFFFAOYSA-N pentyl 4-oxo-3H-phthalazine-1-carboxylate Chemical compound C(CCCC)OC(=O)C1=NNC(C2=CC=CC=C12)=O JPRPQMBRFZKJDW-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- KWVKQEXTPZPDAR-UHFFFAOYSA-N propyl 4-oxo-3h-phthalazine-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OCCC)=NNC(=O)C2=C1 KWVKQEXTPZPDAR-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Cosmetics (AREA)
Description
O
143169
Den foreliggende opfindelse angår en særlig fremgangsmåde til fremstilling af den kendte 4-hydroxymethyl-l-keto--1,2-dihydrophthalazin såvel som syreadditionssalte deraf.
4-Hydroxymethyl-l-keto-l,2-dihydrophthalazin udtrykt 5 ved formlen (I)
CHo0H
r c OO· (i> 10 „ o er en kendt forbindelse med smp. 204°C, jf. "Annual Report of Department of Pharmacy", Kanazawa University, Japan, bind 12, 1-6 (1961). Det har imidlertid hidtil overhovedet 15 ikke været kendt, at denne forbindelse har farmaceutisk virkning. I det ovenfor anførte litteratursted er anført, at forbindelsen med formlen (I) fremstilles ved bromering af o-acetylbenzoesyre, hydrolysering af produktet med en syre og omsætning af hydrolysatet med hydrazin, i overensstemmelse 20 med den i "Ber." 40, 72 (1907) beskrevne metode.
I det nævnte litteratursted anføres intet om den fremstillede forbindelses eventuelle farmaceutiske virkninger eller dens eventuelle anvendelighed. Endvidere anføres det, at forbindelsen med formlen (I) fås i et meget lavt udbytte 25 fra nogle få procent op til 10% ved denne uhensigtsmæssige proces, der omfatter mange trin.
Forbindelsen med formlen (I) har farmaceutisk virkning, især ved behandling, herunder forebyggelse og helbredelse, af blødningstilstande, thrombosis og atherosclero-30 sis, og den har ligeledes lav toksicitet (f.eks.
LD^q>4500 mg/kg mus).
Det har nu vist sig, at forbindelsen med formlen (I) let kan fremstilles i højt udbytte på over 90% ved ifølge opfindelsen at omsætte en forbindelse med formlen (II) 35 2
O
143159
COR
i 5 (II)
II
o i hvilken R er en alkoxygruppe med 1-5 carbonatomer eller et halogenatom, med et alkalimetalborhydrid i et indifferent 1° organisk opløsningsmiddel, og at forbindelsen med formlen (I) danner hidtil ukendte additionssalte med organiske eller uorganiske syrer, hvilke additionssalte har farmaceutiske virkninger, der svarer til virkningerne af forbindelserne med formlen (I) eller er disse overlegne.
15 Det er kendt, at der sædvanligvis anvendes lithium- aluminiumhydrid til fremstilling af en primær alkohol ved reduktion af en carboxylsyreester, og at reaktionen ikke finder sted i væsentlig grad med natriumborhydrid, jf.
"Angew. Chem.", 73, 81 (1961) og H.C. Brown: "Hydroboration" 20 242 (1963). Det er ligeledes velkendt, at den nitrogenholdige heteroring let reduceres ved behandling af en nitrogenholdig heterocyclisk forbindelse, især en diazinforbindelse såsom phthalazin eller quinoxalin med lithiurnaluminiumhydrid, jf. "Jikken Kagaku Koza" eller "Lectures on Experimental 25 Chemistry", bind 17, side 61.
I modsætning til hvad der kunne forventes ud fra den ovennævnte kendte teknik har det nu vist sig, at forbindelsen med formlen (I) kan fremstilles i højt udbytte ved omsætning af forbindelsen med formlen (II) med et alkalimetalborhydrid.
20 Ifølge opfindelsen kan forbindelsen med formlen (I) således fremstilles i højt udbytte ud fra et billigt materiale ved en simpel omsætning, ved hvilken reaktionstrinnene forkortes meget.
Den ved fremgangsmåden ifølge opfindelsen anvendte 25 forbindelse med formlen (II) kan let fremstilles ved en kendt metode. Den kan f.eks. let fremstilles ved den i
O
143159 3 "J. Am. Chem. Soc.", bind 68, side 1316, beskrevne metode ved oxidation af naphthalen med kaliumpermanganat, omsætning af det oxiderede produkt med hydrazin og esterificering af den fremkomne 4-carboxy-l-keto-l,2-dihydrophthalazin ^ på gængs måde eller behandling af denne med thionylchlorid, hvorved den omdannes til syrechloridet.
Som eksempler på forbindelser med formlen (II) kan nævnes 4-methoxycarbonyl-l-keto-l,2-dihydrophthalazin, 4-ethoxycarbonyl-l-keto-l,2-dihydrophthalazin, 4-propoxycar-10 bonyl-l-keto-1,2-dihydrophthalazin, 4-butoxyoarbonyl-l- -keto-1,2-dihydrophthalazin, 4-amyloxycarbony1-1-keto-l,2-dihydrophthalazin , 4-chlorcarbonyl-l-keto-l,2-dihydrophthalazin og 4-bromcarbonyl-l-keto-l,2-dihydrophthalazin.
Som alkalimetalborhydrid kan f.eks. anvendes lithium-15 borhydrid, natriumborhydrid, kaliumborhydrid eller natrium- trimethoxyborhydrid.
Ved fremstilling af forbindelsen med formlen (I) anvendes alkalimetalborhydridet i en mængde på mellem 0,8 og 20 mol, fortrinsvis 1-3 mol pr. mol af forbindelsen med formlen (II), 2° og omsætningen gennemføres i et indifferent organisk opløsningsmiddel. Det har i praksis vist sig hensigtsmæssigt at gennemføre omsætningen i nærværelse af et metalhalogenid såsom calci-umchlorid, magnesiumbromid, lithiumchlorid, lithiumbromid eller lithiumiodid. Når R i formlen (II) er en alkoxygruppe, 25 kan der som opløsningsmiddel anvendes vand eller en C^_g aliphatisk alkohol såsom methanol, ethanol, propanol eller amylalkohol. Det foretrækkes at anvende C^_3-alkoholer.
Når R i formlen (II) er et halogenatom, kan der som opløsningsmiddel anvendes gængse indifferente organiske 30 opløsningsmidler såsom benzen, ethylether, dioxan eller tetrahydrofuran eller blandinger deraf. Når R er et halogenatom, er det tilstrækkeligt at anvende alkalimetalborhydridet i en mængde på ca. 1 til ca. 5 mol pr. mol phthal-azinderivat. Omsætningen kan sædvanligvis gennemføres ved en 35 temperatur i området 0-250°c, fortrinsvis 0-200°C, 4
O
1A3159 helst 0-100°C. Sædvanligvis er reaktionen tilendebragt i løbet af 0,5-3 timer, men reaktionen kan også gennemføres ved lave temperaturer i længere tid. Produktet kan let isole-res og renses.
Fremgangsmåden ifølge opfindelsen illustreres nærmere i de efterfølgende eksempler.
Eksempel 1 *·0 Til en opløsning af NaBH^ i ethanol, fremstillet ved opløsning af 19 g NaBH^ i 120 ml ethanol ved 0-10°C sættes 12 g 4-ethoxycarbonyl-l-keto-l,2-dihydrophthalazin ved 0-10°C under omrøring. Til den således fremstillede suspension sættes en opløsning af 3 g calciumchlorid i 36 ml ethanol, og reaktionsblandingen omrøres i yderligere 5 timer ved stuetemperatur. Ethanolen afdestilleres under formindsket tryk, og remanensen opløses i vand. Opløsningens pH-værdi indstilles på 6-7 med eddikesyre, og der tørres under formindsket tryk. Remanensen ekstraheres kontinuert med chloroform under Π anvendelse af et Soxhlet-apparat. Chloroformekstrakten afdestilleres, og remanensen omkrystalliseres af methanol, hvorved der fås 4-hydroxymethyl-l-keto-l,2-dihydrophthala-zin med smp. 206-208°C. Produktudbyttet er 8,6 g (90%).
25 UV-spektrum: Λ 225 ηιμ (e=l6.100), 245 ηιμ (e=7*T00),
IIlcwC
253 πιμ (e=8.200), 2θ1 ιημ (ε=β.4θθ), 300 πιμ (e=4.500), 312 πιμ (e=2.800).
Eksempel 2 30 En blanding af 3 g 4-carboxy-l-keto-l,2-dihydrophthal- azin og 40 ml thionylchlorid tilbagesvales forsigtigt ved 70-80°C i 1 time på et vandbad. Overskud af thionylchlorid afdestilleres derpå, og remanensen opløses i 30 ml dioxan.
Til dioxanopløsningen sættes portionsvis 2 g natriumborhy-35 drid ved 0-10°C under omrøring. Reaktionsblandingen omrøres i yderligere 1 time, og derpå afdestilleres opløsningsmidlet.
O
143159 5
Remanensen omkrystalliseres af vand, hvorved der fås 4-hydroxymethyl-l-keto-l,2-dihydrophthalazin med smp. 201-202°C. Produktudbyttet er 2,1 g (70%),
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP46058643A JPS5116430B2 (da) | 1971-08-05 | 1971-08-05 | |
| JP5864371 | 1971-08-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK143159B true DK143159B (da) | 1981-07-06 |
| DK143159C DK143159C (da) | 1981-11-16 |
Family
ID=13090247
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK366572A DK131857C (da) | 1971-08-05 | 1972-07-24 | Analogifremgangsmade til fremstilling af 4-hydroxymethyl-1-phthalazonderivater eller syreadditionssalte deraf |
| DK377872A DK143159C (da) | 1971-08-05 | 1972-07-31 | Fremgangsmaade til fremstilling af 4-hydroxymethyl-1-keto-1,2-dihydrophthalazin eller syreadditionssalte deraf |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK366572A DK131857C (da) | 1971-08-05 | 1972-07-24 | Analogifremgangsmade til fremstilling af 4-hydroxymethyl-1-phthalazonderivater eller syreadditionssalte deraf |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US3864343A (da) |
| JP (1) | JPS5116430B2 (da) |
| AR (3) | AR197089A1 (da) |
| AT (2) | AT317233B (da) |
| AU (2) | AU461281B2 (da) |
| BE (2) | BE787139A (da) |
| CA (2) | CA999236A (da) |
| CH (2) | CH577980A5 (da) |
| CS (2) | CS180588B2 (da) |
| DE (2) | DE2237832A1 (da) |
| DK (2) | DK131857C (da) |
| ES (2) | ES405456A1 (da) |
| FR (2) | FR2150736B1 (da) |
| GB (2) | GB1404368A (da) |
| HU (2) | HU163726B (da) |
| IE (2) | IE36598B1 (da) |
| LU (2) | LU65856A1 (da) |
| NL (2) | NL7210369A (da) |
| NO (1) | NO134113C (da) |
| SE (2) | SE408177B (da) |
| SU (2) | SU577986A3 (da) |
| YU (1) | YU35245B (da) |
| ZA (2) | ZA725203B (da) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR205004A1 (es) * | 1973-10-30 | 1976-03-31 | Ishikawa M | Procedimiento para preparar derivados de 6,8-dialquil-7-alcoxi-carbonil-4-hidroximetil-1-ftalazona y la 7,8-lactona |
| NL7702763A (nl) * | 1976-03-18 | 1977-09-20 | Takio Shimamoto En Masayuki Is | Werkwijze voor de bereiding van thromboxaan- -antagonisten en van preparaten die deze stof- fen bevatten. |
| IE47592B1 (en) * | 1977-12-29 | 1984-05-02 | Ici Ltd | Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof,and process for their manufacture |
| US4293553A (en) * | 1978-08-11 | 1981-10-06 | Masayuki Ishikawa | 1-Phthalazone derivatives, and use thereof |
| US4861778A (en) * | 1986-06-16 | 1989-08-29 | Research Corporation | 2,3-dihydrophthalazine-1,4-diones |
| CH683965A5 (it) * | 1993-02-19 | 1994-06-30 | Limad Marketing Exp & Imp | Composti della classe dei ftalidrazidici come sostanza attiva in agenti antinfiammatori ed antitossici. |
| DE102005011822A1 (de) * | 2005-03-15 | 2006-09-21 | Merck Patent Gmbh | Phthalazinone |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE687916A (da) * | 1965-10-12 | 1967-03-16 |
-
1971
- 1971-08-05 JP JP46058643A patent/JPS5116430B2/ja not_active Expired
-
1972
- 1972-07-21 AU AU44843/72A patent/AU461281B2/en not_active Expired
- 1972-07-24 US US275171A patent/US3864343A/en not_active Expired - Lifetime
- 1972-07-24 AR AR243236A patent/AR197089A1/es active
- 1972-07-24 DK DK366572A patent/DK131857C/da not_active IP Right Cessation
- 1972-07-24 AR AR243235A patent/AR194123A1/es active
- 1972-07-25 IE IE1047/72A patent/IE36598B1/xx unknown
- 1972-07-25 GB GB3482072A patent/GB1404368A/en not_active Expired
- 1972-07-25 GB GB3482172A patent/GB1404367A/en not_active Expired
- 1972-07-25 IE IE1046/72A patent/IE36597B1/xx unknown
- 1972-07-25 AU AU44940/72A patent/AU461018B2/en not_active Expired
- 1972-07-27 ZA ZA725203A patent/ZA725203B/xx unknown
- 1972-07-27 NL NL7210369A patent/NL7210369A/xx unknown
- 1972-07-27 ZA ZA725202A patent/ZA725202B/xx unknown
- 1972-07-27 NL NL727210370A patent/NL151261B/xx not_active IP Right Cessation
- 1972-07-28 SE SE7209886A patent/SE408177B/xx unknown
- 1972-07-31 DK DK377872A patent/DK143159C/da not_active IP Right Cessation
- 1972-08-01 DE DE2237832A patent/DE2237832A1/de active Pending
- 1972-08-02 ES ES405456A patent/ES405456A1/es not_active Expired
- 1972-08-03 BE BE787139A patent/BE787139A/xx not_active IP Right Cessation
- 1972-08-03 BE BE787138A patent/BE787138A/xx not_active IP Right Cessation
- 1972-08-03 SE SE7210119A patent/SE406587B/xx unknown
- 1972-08-03 YU YU2013/72A patent/YU35245B/xx unknown
- 1972-08-03 SU SU7201817033A patent/SU577986A3/ru active
- 1972-08-04 HU HUIO185A patent/HU163726B/hu unknown
- 1972-08-04 ES ES405555A patent/ES405555A1/es not_active Expired
- 1972-08-04 NO NO2793/72A patent/NO134113C/no unknown
- 1972-08-04 LU LU65856A patent/LU65856A1/xx unknown
- 1972-08-04 HU HUIO186A patent/HU165815B/hu unknown
- 1972-08-04 LU LU65855A patent/LU65855A1/xx unknown
- 1972-08-04 DE DE2238566A patent/DE2238566A1/de active Pending
- 1972-08-04 SU SU1814854A patent/SU513622A3/ru active
- 1972-08-04 CS CS7200005458A patent/CS180588B2/cs unknown
- 1972-08-04 CA CA148,813A patent/CA999236A/en not_active Expired
- 1972-08-04 CH CH1160472A patent/CH577980A5/xx not_active IP Right Cessation
- 1972-08-04 FR FR7228258A patent/FR2150736B1/fr not_active Expired
- 1972-08-04 AT AT06734/72A patent/AT317233B/de not_active IP Right Cessation
- 1972-08-04 CA CA148,812A patent/CA966489A/en not_active Expired
- 1972-08-04 CH CH1160372A patent/CH580081A5/xx not_active IP Right Cessation
- 1972-08-04 FR FR7228257A patent/FR2150735B1/fr not_active Expired
- 1972-08-04 AT AT852473A patent/AT320658B/de not_active IP Right Cessation
- 1972-08-04 CS CS7200005457A patent/CS180587B2/cs unknown
-
1973
- 1973-08-14 AR AR249572A patent/AR197156A1/es active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH03115265A (ja) | ピラゾール及びその誘導体の製造方法 | |
| DK143159B (da) | Fremgangsmaade til fremstilling af 4-hydroxymethyl-1-keto-1,2-dihydrophthalazin eller syreadditionssalte deraf | |
| Gilman et al. | Orientation in the Furan Nucleus. VI. β-Substituted Furans | |
| McManus et al. | Tetrazole analogs of plant auxins1 | |
| USRE28242E (en) | Method for manufacturing tetronic acid | |
| US4284797A (en) | Process for separating mixtures of 3- and 4-nitrophthalic acid | |
| Arnold et al. | A Study of the Haloform Reaction | |
| US4287348A (en) | Preparation of sulphoalkyl quaternary salts | |
| CA1128952A (en) | Process for the preparation of a carbazole derivative | |
| US3457314A (en) | Alpha-bromo-cinnamaldehydes and process for preparing them | |
| CH445492A (de) | Verfahren zur Herstellung von in 1-Stellung acylierten a-(3-Indolyl)-niederaliphatischen-säuren | |
| SU541428A3 (ru) | Способ получени простых гликолевых эфиров | |
| FLEIFEL | Bromination and Iodination of Some p-Alkylbenzoic Acids | |
| US3549657A (en) | N-aryl-4,6-dibromo-3-hydroxyphthalimide derivatives | |
| US2513140A (en) | 3-thienylacetic acid | |
| GB588377A (en) | Improvements in and relating to the production of furan derivatives | |
| US3598844A (en) | Azidocinnamic aldehydes | |
| Ternay Jr et al. | Borohydride reduction of thioxanthone sulfoxide. Base-induced dehydration of thioxanthenol sulfoxide | |
| SU334806A1 (ru) | Способ получени 3-оксиметилроданинов | |
| US2447626A (en) | Beta-diketones and process for preparing them | |
| US4219482A (en) | Process for preparing thiophene and furan derivatives | |
| US3530188A (en) | Bromomethylbenzophenones and related compounds | |
| SU1143745A1 (ru) | Способ получени производных 3-(3-бензоксазолонил)пропановой кислоты | |
| US2964565A (en) | Method of separating octahalocyclohexene-3-one-1 from mixtures containing said compound and octahalocyclohexene-2-one-1 | |
| JPS5916878A (ja) | ２，４−ジヒドロキシ−３−アセチルキノリン類の製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |