NO821086L - PROCEDURE FOR PREPARING 8- (4- (4- (2-PYRIMIDINYL) -1-PIPERAZINYL) -BUTYL) -8-AZASPIRO (4,5) DECAN-7,9-DION - Google Patents
PROCEDURE FOR PREPARING 8- (4- (4- (2-PYRIMIDINYL) -1-PIPERAZINYL) -BUTYL) -8-AZASPIRO (4,5) DECAN-7,9-DIONInfo
- Publication number
- NO821086L NO821086L NO821086A NO821086A NO821086L NO 821086 L NO821086 L NO 821086L NO 821086 A NO821086 A NO 821086A NO 821086 A NO821086 A NO 821086A NO 821086 L NO821086 L NO 821086L
- Authority
- NO
- Norway
- Prior art keywords
- compound
- formula
- azaspiro
- butyl
- pyrimidinyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 title claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 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 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- -1 sodium Chemical class 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- BCNBRBQCDHLCBD-UHFFFAOYSA-N 8-(4-chlorobutyl)-8-azaspiro[4.5]decane-7,9-dione Chemical compound C1C(=O)N(CCCCCl)C(=O)CC11CCCC1 BCNBRBQCDHLCBD-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 2
- XBVZKHPTGUWNEH-UHFFFAOYSA-N 2-[4-(4-chlorobutyl)piperazin-1-yl]pyrimidine Chemical compound C1CN(CCCCCl)CCN1C1=NC=CC=N1 XBVZKHPTGUWNEH-UHFFFAOYSA-N 0.000 description 2
- BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229960002495 buspirone Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N 1-butanol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- FWPVKDFOUXHOKQ-UHFFFAOYSA-N 2-[1-(carboxymethyl)cyclopentyl]acetic acid Chemical compound OC(=O)CC1(CC(O)=O)CCCC1 FWPVKDFOUXHOKQ-UHFFFAOYSA-N 0.000 description 1
- WBRXGQPUYZLAFA-UHFFFAOYSA-N 4-chlorobutyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCCCl)C=C1 WBRXGQPUYZLAFA-UHFFFAOYSA-N 0.000 description 1
- HUNFFPQEYDANPE-UHFFFAOYSA-N 4-chlorobutyl methanesulfonate Chemical compound CS(=O)(=O)OCCCCCl HUNFFPQEYDANPE-UHFFFAOYSA-N 0.000 description 1
- GFWLMILMVMCJDI-UHFFFAOYSA-N 8-oxaspiro[4.5]decane-7,9-dione Chemical compound C1C(=O)OC(=O)CC11CCCC1 GFWLMILMVMCJDI-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
Denne oppfinnelse angår en ny fremgangsmåte for fremstilling av 8-(4-(4-(2-pyrimidinyi)-1-piperazinyl) -butyl) -8-azaspiro(4,5)dekan-7,9-dion (I). This invention relates to a new process for the preparation of 8-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-8-azaspiro(4,5)decane-7,9-dione (I).
Fremgangsmåten karakteriseres ved at forbindelsen med formel II hvor M er et alkalimetall såsom natrium, omsettes med en forbindelse med formel III hvor X, er et halogenatom såsom klor, og R er en alkyl- eller arylgruppe, såsom metyl eller p-tolyl, til en forbindelse med formel IV som på i og for seg kjent måte omsettes med en forbindelse med formel V. The method is characterized in that the compound of formula II where M is an alkali metal such as sodium is reacted with a compound of formula III where X is a halogen atom such as chlorine, and R is an alkyl or aryl group, such as methyl or p-tolyl, to a compound of formula IV which is reacted in a manner known per se with a compound of formula V.
Forbindelsen med formel I, som også kjennes under navnet buspiron, er et kjent legemiddel. Fra U.S. patent 3 717 634 kjennes en fremgangsmåte for fremstilling derav, hvor 8-oksa-spiro(4,5)-dekan-7,9-dion omsettes med 4-amino-l-butanol til 8-(4-hydroksybutyl) -8-azaspiro (4 , 5) dekan-7 ,'9-dion, som om-vandles til 8-(4-klorbutyl)-8-azaspiro(4,5)dekan-7,9-dion (IV), som til slutt omsettes med 1-(2-pyrimidinyl)-piperazin (V). The compound of formula I, which is also known under the name buspirone, is a known drug. From the U.S. patent 3 717 634 discloses a method for its preparation, where 8-oxa-spiro(4,5)-decane-7,9-dione is reacted with 4-amino-1-butanol to 8-(4-hydroxybutyl)-8- azaspiro (4,5)decane-7,'9-dione, which is converted to 8-(4-chlorobutyl)-8-azaspiro(4,5)decane-7,9-dione (IV), which finally is reacted with 1-(2-pyrimidinyl)-piperazine (V).
Fremgangsmåten for fremstilling av mellomproduktet IV, som hører til denne kjente fremgangsmåte, er imidlertid ikke tilfredsstillende med tanke på industriell produksjon, ettersom utbyttet er ganske lavt (ca. 40%), og etter de to faser av fremgangsmåten bør produktene renses ved destillasjon i høyvakuum. Dessuten er 4-amino-l-butanol, som anvendes som det ene utgangsstoff, særskilt vanskelig å fremstille og er dyr. However, the method for producing the intermediate IV, which belongs to this known method, is not satisfactory from the point of view of industrial production, as the yield is quite low (approx. 40%), and after the two phases of the method the products should be purified by distillation in a high vacuum . Furthermore, 4-amino-1-butanol, which is used as the starting material, is particularly difficult to produce and is expensive.
I U.S. patent 3 717 6 34 ér også beskrevet en fremgangsmåte hvor en forbindelse med formel II omsettes•med 1-(4-klor-butyl) -4- (2-pyrimidinyl) piperazin. Dette kommer imidlertid ikke på tale i praksis, ettersom 1-(4-klorbutyl)-4-(2-pyrimi-dinyl) piperazin ikke er en stabil forbindelse, men ringslut-ter seg spontant til en kvartær arttmoniumf orbindelse. In the U.S. patent 3 717 6 34 also describes a method in which a compound of formula II is reacted with 1-(4-chloro-butyl)-4-(2-pyrimidinyl)piperazine. However, this is out of the question in practice, as 1-(4-chlorobutyl)-4-(2-pyrimidinyl)piperazine is not a stable compound, but ring-closes spontaneously to a quaternary ammonium compound.
Det er nå funnet at forbindelsen med formel IV kan fremstilles merkbart enklere og med særdeles godt utbytte når 8-alkalimetall-8-azaspiro(4,5)dekan-7,9-dion (II) omsettes med 4-halogen-l-butylalkyl(eller aryl)-sulfonat (III). Som alkali-. metall anvendes fordelaktig natrium og som halogen klor* Av. sulfonatene kommer særlig på tale metansulfonatet og p-toiylsulfonatet. Omsetningen utføres fordelaktig i et polart,- aprotisk oppløsningsmiddel såsom N,N-dimetylformamid eller N,N-dimetylacetamid, ved,50-15D°C, mest fordelaktig ved ca. 8 0°C. It has now been found that the compound of formula IV can be prepared noticeably more easily and with particularly good yield when 8-alkali metal-8-azaspiro(4,5)decane-7,9-dione (II) is reacted with 4-halo-1-butylalkyl (or aryl)-sulfonate (III). As alkali-. metal is advantageously used sodium and as a halogen chlorine* Av. the sulphonates include methane sulphonate and p-toyl sulphonate in particular. The reaction is advantageously carried out in a polar, aprotic solvent such as N,N-dimethylformamide or N,N-dimethylacetamide, at 50-15°C, most advantageously at approx. 80°C.
Det er kjent å fremstille forbindelser med formel III fra R-sulfonsyreklorid og 4-halogen-l-butanol. ved å utføre omsetningen i pyridin (Can. J. Chem. 3jL (1956) 757) . Det er imidlertid mer fordelaktig å anvende et inert organisk oppløs-ningsmiddel og minst en ekvimolar mengde tertiært amin. Særlig kommer métylenklorid og trietylamin på tale. It is known to prepare compounds of formula III from R-sulfonic acid chloride and 4-halo-1-butanol. by carrying out the reaction in pyridine (Can. J. Chem. 3jL (1956) 757). However, it is more advantageous to use an inert organic solvent and at least an equimolar amount of tertiary amine. In particular, methylene chloride and triethylamine are mentioned.
Forbindelsen med formel II kan fremstilles for eksempel ved å bringe 3,3-tetrametylenglutarsyre til å reagere med urinstoff til det tilsvarende imid og. dette videre med alkali-metallalkoksyd til forbindelsen med formel II, The compound of formula II can be prepared, for example, by reacting 3,3-tetramethyleneglutaric acid with urea to the corresponding imide and. this further with alkali metal alkoxide to the compound of formula II,
Følgende eksempel illustrerer oppfinnelsen.The following example illustrates the invention.
Eksempel 1. 8-(4-klorbutyl)-8-azaspiro(4,5)dekan-7,9-dion En blanding som inneholder 12u g (0,63 mol.) 8-natrium-8-azaspiro(4,5)dekan-7,9-dibn og 165 g (0,63 mol) 4-klorbutyl-p-toluensulfonat (eller 118 g 4-klorbutylmetansulfonat) i ■ 700 ml N,N-dimetylformamid (eller N,N-dimetylacetamid), opp-varmes under omrøring i 2 timer ved 80°C Blandingen nedkjø-les til 20°C og filtreres. Oppløsningsmidlet fjernes under nedsatt trykk. Til den flytende resten settes 1000 ml mety-lenklorid, og den oppnådde oppløsning.vaskes 2 ganger med 500 ml. 0,5 N NaOH-oppløsning og 2 ganger med 500 ml vann.-Oppløsningsmidlet fjernes under nedsatt trykk hvorved 140^- ' Example 1. 8-(4-Chlorobutyl)-8-azaspiro(4,5)decane-7,9-dione A mixture containing 12 µg (0.63 mol.) of 8-sodium-8-azaspiro(4,5 )decane-7,9-dibn and 165 g (0.63 mol) 4-chlorobutyl-p-toluenesulfonate (or 118 g 4-chlorobutylmethanesulfonate) in ■ 700 ml N,N-dimethylformamide (or N,N-dimethylacetamide), heated with stirring for 2 hours at 80°C. The mixture is cooled to 20°C and filtered. The solvent is removed under reduced pressure. 1000 ml of methylene chloride is added to the liquid residue, and the resulting solution is washed twice with 500 ml. 0.5 N NaOH solution and 2 times with 500 ml of water.-The solvent is removed under reduced pressure whereby 140^- '
148 g (85-90%) ønsket produkt oppnås som en oljelignende væske. 1H-NMR . (CDC13) : 6 1,6 (12H,m) 2,5 (4H,s) , .3,5 (2H,t), 148 g (85-90%) of the desired product is obtained as an oil-like liquid. 1H-NMR. (CDCl 3 ) : 6 1.6 (12H,m) 2.5 (4H,s) , .3.5 (2H,t),
3,75 (2H,t).. 3.75 (2H,t)..
Eksempel 2.. 8- (4-(4-( 2-pyrimidihyl) -1-piperazinyl) -butyl) - 8-azaspiro(4,5)dekan-7,9-dion (buspiron) Example 2.. 8-(4-(4-(2-pyrimidyl)-1-piperazinyl)-butyl)-8-azaspiro(4,5)decane-7,9-dione (buspirone)
En blanding som .inneholder 50,0 g (0,19 mol) 8-(4-klor-butyl)-8-azaspiro(4,5)dekan-7,9-dion, 31,8 g (0,19 mol)" 1- (2-pyrimidinyl)piperazin og 4l g natriumkarbonat i 300 ml N,N-dimetylformamid tilbakeløpsbehåndles i 18 timer. Opp-løsningen filtreres, og oppløsningsmidlet fjernes under nedsatt trykk. Den oljelignende resten krystalliseres fra 2- propanol, hvorved man får 5 8,3 g 85% ønsket produkt som farveløse krystaller (sm.p. 109-110°G). ^H-NMR (CDC13): 6 1,5 (12H,m), 2,45 (6h,t), 2,55 (4H,s), 3,75 (6H,m), 6,4 (1H,t) , '8,25 (2H,d) . A mixture containing 50.0 g (0.19 mol) 8-(4-chloro-butyl)-8-azaspiro(4,5)decane-7,9-dione, 31.8 g (0.19 mol )" 1-(2-pyrimidinyl)piperazine and 4l g of sodium carbonate in 300 ml of N,N-dimethylformamide are refluxed for 18 hours. The solution is filtered, and the solvent is removed under reduced pressure. The oil-like residue is crystallized from 2-propanol, whereby gives 5 8.3 g 85% of the desired product as colorless crystals (m.p. 109-110°G). ), 2.55 (4H,s), 3.75 (6H,m), 6.4 (1H,t) , '8.25 (2H,d) .
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI811108 | 1981-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO821086L true NO821086L (en) | 1982-10-11 |
Family
ID=8514296
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO821086A NO821086L (en) | 1981-04-09 | 1982-03-31 | PROCEDURE FOR PREPARING 8- (4- (4- (2-PYRIMIDINYL) -1-PIPERAZINYL) -BUTYL) -8-AZASPIRO (4,5) DECAN-7,9-DION |
Country Status (3)
| Country | Link |
|---|---|
| DK (1) | DK152730C (en) |
| NO (1) | NO821086L (en) |
| SE (1) | SE449224B (en) |
-
1982
- 1982-03-31 NO NO821086A patent/NO821086L/en unknown
- 1982-04-02 SE SE8202132A patent/SE449224B/en not_active IP Right Cessation
- 1982-04-07 DK DK160082A patent/DK152730C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE8202132L (en) | 1982-10-10 |
| SE449224B (en) | 1987-04-13 |
| DK152730B (en) | 1988-05-02 |
| DK152730C (en) | 1988-10-03 |
| DK160082A (en) | 1982-10-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR820002136B1 (en) | Process for preparing 2-amino pyrimidones | |
| RU2174978C2 (en) | Method of synthesis of pyrimidine derivative, intermediate compounds and method of their synthesis | |
| KR20020000167A (en) | Process for the Preparation of Substituted Pyrimidines | |
| NO821086L (en) | PROCEDURE FOR PREPARING 8- (4- (4- (2-PYRIMIDINYL) -1-PIPERAZINYL) -BUTYL) -8-AZASPIRO (4,5) DECAN-7,9-DION | |
| JP3252502B2 (en) | N-5 protected 2,5-diamino-4,6-dichloropyrimidine and method for producing the same | |
| JP2762430B2 (en) | Preparation of aralkylaminopyrimidines | |
| US5266697A (en) | Process for the production of 2-substituted 4,6-dialkoxypyrimidines | |
| US4900827A (en) | Process for the preparation of pyrimidine derivatives | |
| US20020004600A1 (en) | Process for the preparation of substituted pyrimidines | |
| CA1208213A (en) | Process for producing heterocyclic compound having nitromethylene group as the side chain group | |
| US6673925B2 (en) | Method of producing thiobarbituric acid derivatives | |
| FI72975B (en) | FOR EXAMINATION OF FRAMSTAELLNING AV 8- (4- (4- (2-PYRIMIDINYL) -1-PIPERAZINYL) BUTYL) -8-AZASPIRO (4,5) DECANE-7,9-DION. | |
| EP0293742A1 (en) | Process for the production of 4-nitro-5-imidazolylethers and -thioethers | |
| NO783775L (en) | 2,4-DIAMINO-5-BENZYLPYRIMIDINES AND PROCEDURES FOR THE PREPARATION OF THESE | |
| US5208337A (en) | Process for the preparation of aminopyrimidines | |
| EP0102157B1 (en) | Amino pyrimidinones and their preparation | |
| EP0066440B1 (en) | Chemical process | |
| US4294970A (en) | Oxidation of alpha-alkylated, benzyl-substituted 2-thiopyridine 1-oxides | |
| EP1440063B1 (en) | Process for the preparation of 1-(pyrimidin-2-yl)propan-2-ones | |
| WO1999044969A1 (en) | Methods for highly selectively o-alkylating amide compounds with the use of copper salts | |
| NO781587L (en) | BENZYLPYRIMIDINES AND METHODS FOR THE PREPARATION OF THESE | |
| JPH0655711B2 (en) | Method for producing cyanoguanidine derivative | |
| JPH0273055A (en) | Production of substituted quanylthiourea | |
| EP0092903A2 (en) | Process for preparing 2-pyridylalkyl amines | |
| SK142195A3 (en) | Preparation of symetrical or unsymetrical disubstituted n-cyanoditioimino-carbonates |